فهرست مطالب emad behboudi

The most extensive monkeypox outbreak in history commenced in 2022 and has swiftly disseminated globally. This review aims to succinctly outline host immune reactions to orthopoxviruses, present an insight into available vaccines to counteract the epidemic, and delve into clinical research and animal studies examining induced immunity against monkeypox induced via the vaccinia virus-based monkeypox vaccines. It addresses current concerns about the outbreak and suggests optimal vaccine utilization as a control measure. During the 1980s, surveillance studies in Central Africa and subsequent outbreaks demonstrated that smallpox vaccines were approximately 85% effective against monkeypox. These findings are substantiated by numerous animal studies, primarily in primates, involving live virus challenges through different inoculation methods, consistently showcasing high levels of protection and immunity post-vaccination. Smallpox vaccines emerge as effective countermeasures for managing monkeypox outbreaks, although they do entail adverse effects, and second-generation, replicative vaccines have prohibited usage. Third-generation vaccines pose a challenge for rapid responses as they require 2 doses, which can be difficult for people with weak immunity.  Insights from the COVID-19 outbreak must guide our collective approach to addressing the monkeypox outbreak and future outbreaks.

Hepatocellular carcinoma (HCC) is recognized as one of the most deadly malignant cancers which ranks third among all annual cancer mortality rates. The hepatitis B virus (HBV) X protein (HBX) is known to play a key role in HCC. The HBX may alter the expression of multiple microRNAs (miRs), which are important in hepatocarcinogenesis. This study aimed to investigate the importance of HBX protein in mir21, mir22, mi122, mir132, and mir222 expression. In the present study, a recombinant vector, pcDNA3.1+ expressing HBx was developed. The Huh-7 cell line was transfected with HBx-pcDNA3.1+ recombinant plasmid. Real-Time Polymerase Chain Reaction was used to evaluate mir21, mir22, mi122, mir132, and mir222 expression in the cell line. It was found that expression of miR-21 and miR-222 was upregulated at all points of time since HBx transfection. The expression of miR-21 reached to 4.24-fold after 72 hours post-transfection. The miR-22 had a 7.69-fold downregulation after 24 hours. The miR-122 had a significant downregulation after 48 (10-fold) hours. The miR-132 expression reached its lowest rate at 12 hours after HBx-transfection (8.33-fold). The miR-222 expression was upregulated in transfected cells but was not significantly different (1.18 to 2.45-fold). Significant downregulation of miR-22, miR-122 and miR-132 implicate their inhibitory roles in the progression of HBV-associated HCC. The expression of these microRNAs could be used as a prognosis of the progression of HBV-associated liver disease. Also, in future studies, miR-21 and miR-22 can be used as a target in the development of therapeutic agents.

The Human papillomaviruses (HPV) main capsid protein L1 is naturally capable to self-assemble as virus-like particles (VLPs). There are different recombinant protein expression systems such as bacteria, yeast, insect, plant, and mammalian cells for generation of VLP-based candidate vaccines targeting various pathogens. In this study, we produced HPV-L1 protein by BL21/pET32a expression system and VLP production was confirmed.

The recombinant plasmid pET32/L1 was transformed into Escherichia. coli BL21 and selected with ampicillin. The positive clones containing the recombinant plasmid pET32/L1 were assessed by restriction endonucleases HindIII and XhoI and sequence analysis. The expression of HPV16-L1 fusion protein in E. coli BL21was identified by SDS-PAGE and Western blotting. VLPs were evaluated using electron microscopy.

A codon-optimized L1 gene was expressed in BL21 under the control of the T7/lac promoter. Purification of L1 protein was achieved after Ni NTA chromatography. The 60kDa protein was detected in the lysates of BL21, recognized as HPV16- L1 protein by Western blotting. VLPs were confirmed using electron microscopy.

In this study, we established a high-efficient recombinant E. coli expression system for the production of HPV 16- L1 protein. The generated L1 protein was correctly self-assembled into VLPs. Therefore, BL21/pET32a as a prokaryotic expression system is a potent tool for HPV16-L1 VLP production.

Dear Editor, At the end of 2020, variants of the SARS-CoV-2 virus appeared as a great risk to public’s health and therefore, in order to prioritize global monitoring and research, they were placed in the category of variants of interest (VOIs), variants of concern (VOCs) and under monitoring variants (VUMs). As of April 2022, omicron (B.1.1.529) sub-variants of SARS-CoV-2, including BA.2.12.1, BA.4, and BA.5, are considered variants of concern with increased virulence and transmissibility. The omicron variant of SARS-CoV-2 is emerging in communities where people have already been infected with earlier variants and are now vaccinated, or people who have received two or three doses of the coronavirus vaccination. More than 130 countries worldwide have implemented booster programs to combat omicron. Despite preliminary findings that suggest booster doses may improve omicron protection, more research is needed to prove this. In the case of the COVID-19, it was recommended that at least 2 injections of the vaccine be given, and after 6 months we saw a decline in immunity. Taken together, the studies suggest that the BQ and XBB subtypes pose serious threats to current vaccines, inactivate all neutralizing antibodies, and may have spread in the population due to their evolution in evading antibodies. Though people still need to take this issue seriously and protect themselves.

There is minimal data on the effects of COVID-19 on male fertility, so it has become an important topic for investigation. The coronavirus (SARS-CoV-2) can damage the testicles as well as the male reproductive system through various mechanisms and cause infertility in men. In a study ‘in situ hybridization’ did not detect the viral genome in testicular tissue samples. This suggests that the testicular damage was probably due to the inflammatory and immune response and not due to direct damage by the virus. Therefore, there is a possibility of testicular damage and subsequent infertility following a COVID-19 infection. Testicular damage can be caused either by direct viral invasion by binding the SARS-COV2 virus to ACE2 receptors or by an immune and inflammatory response. Follow-up studies of the reproductive function of recovered male patients are needed to investigate this possibility.

Recently in a review article by Mansourabadi et al. published in the Iranian Journal of Immunology, the authors described the serological and molecular tests for COVID-19 (1). The mentioned review considered helicase (Hel) as a structural protein of SARS-CoV-2 (1). However, based on evidence, the genome of novel coronavirus is approximately 30kb in length and encodes only four structural proteins, including spike (S), envelope (E), membrane (M), and nucleoprotein (N) (2, 3), although helicase (NSP13) as a nonstructural protein such as RNA-dependent RNA polymerases (NSP12) encoded by the ORF region and is involved in the replication of the virus (3). In addition, authors reported that hemagglutinin esterase could be used as a favorite target for SARS-CoV-2 Real-time PCR (1); however, scientific evidence shows that SARS-CoV-2 as a betacoronavirus lineage B like SARS-CoV lacks hemagglutinin esterase (4-6); thus this protein cannot be a target for detection of SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) provokes the host immune responses and induces severe respiratory syndrome by overreaction of immune cells. IL-1β is a pro-inflammatory cytokine highly associated with the related inflammation and cytokine storm, and several IL-1β antagonists are being used to treat cytokine release syndrome (CRS). Accordingly, some studies and clinical trials are investigating the effects of IL-1β antagonists for controlling Coronavirus disease 2019 (COVID-19) associated CRS. Here, we will review any interaction and association between IL-1β and SARS-CoV-2 infection.

Molecular analysis of SARS-CoV-2 genome is important to predict viral pathogenicity. In addition to transmission, replication is a key factor in pathogenicity of the virus. Notably, mutations in non-structural proteins (NSP3 and NSP12) can affect host immune response and viral replication. Therefore, this study was conducted to investigate different mutations of SARS-CoV-2 NSP3, and NSP12 during different waves of COVID-19 infection.

We recruited 57 NGS sequences including 8 NGS sequences from Golestan SARS-CoV-2 RNA samples, obtained as part of clinical testing in different referral centers of Iran. After obtaining sequences from the global initiative on sharing all influenza data (GISAID), and evaluating and processing data, all sequences were aligned to the Wuhan variant genome (NC_045512.2) using MEGA6. The HDOCK server was used for molecular docking.

In NSP3, mutations in positions (nts 315, 545, 2666, 3264) were more frequent and among them mutation in positions including nt 545 (aa182) and nt 2666 (aa889) were associated with an increase in codon usage. In the term of NSP12, mutations in positions such as nts 406 (aa137), 965 (aa323), 1233, 1653, 1836, 2733 were more frequent. The molecular docking results showed more affinity in some variants of NSP3 and NSP12 as well.

This study has assessed mutation in SARS-CoV-2 Nsp3, and NSP12 which are viral protease, and viral polymerase (RdRp). The mutations reported in this study may help this virus to replicate faster and evade the pharmaceutical agents which target viral polymerase activity and be very effective in viral pathogenesis. In addition, this study highlights the importance of ongoing genomic variation studies to be performed on SARS-CoV-2 variants.

Dear Editor The current epidemic of the novel Coronavirus disease 2019 (COVID-19) risen from Wuhan, China, turned to a worldwide concern because of its incubation period (2-14 days) and its high transmission rate. The first cases of the infection were reported in December 2019 in Wuhan with symptoms like pneumonia with an unknown reason. Very soon it was known as a novel kind of Coronavirus on 31 December 2019. severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the main viral agent of this disease, is belonging to betacoronavirus genera, Coronaviridae family, an enveloped positive sense RNA virus. Like SARS-CoV, SARS-CoV-2 attacks the organism by binding to the angiotensin-converting enzyme 2 (ACE2). Recently, some reports of SARS-CoV-2 infection have been shown that the virus is found not only in the respiratory tract but also in the gastrointestinal tract. In recent year, SARS-CoV-2 is still infecting populations that lack immunity to the virus, causing significant disease and mortality (1, 2). Immunity to SARS-CoV-2, either through natural infection or through vaccination, to some extent protects and reduces the risk of significant clinical consequences. For example, it has been estimated that improved seropositive individuals can have up to 89% protection against re-infection (3) and that vaccine efficacy has been reported to be 50 to 95% (4). However, the duration of the created immunity period is not known and over time, this immunity weakens (5, 6), in addition, there is concern about the escape of new variants from the immune system (7). An important question here is to identify the immune link with protection against SARS-CoV-2 and thus predict how these changes will affect the clinical outcome of the disease. Neutralizing antibody titer is an important predictor of the effectiveness of vaccines in development. Studies show that the level of neutralizing antibodies decreases over time and a booster may be needed within a year. However, protection against the severe form of the disease may be significantly longer. It can be said that the development of a strong or weak humoral response depends on the interaction of the virus and the host and the inflammation that occurs. If the challenge is low, the antibody produced has poor performance, but if the challenge is high, the antibody produced is more functional and responds more aggressively to re-exposure to the pathogen. In addition, cellular immune responses can play a prominent role in this regard (8). Therefore, if existing vaccines, such as natural infections, are able to stimulate the cellular immune response in addition to producing neutralizing antibodies, the immunity persistence of the vaccine will also increase. Another question that arises is whether determining the antibody titer after a natural infection or vaccination can be a correct marker of the state of protection against infection? Antibodies act as markers of infection and, if persisted, can lead to long-term immunity. In most clinically approved vaccines we measure the binding antibody titer, while this is a neutralizing antibody titer that indicates how immunogenic is a vaccine. An antibody, in addition to binding to the desired antigen, must also be able to neutralize that antigen, either by blocking the infection by preventing the pathogen from binding to the receptor or by stimulate immune cells for clearance and disease control, which should also be considered in vaccine studies. In addition to antibody titer and function, knowing how antibody function is related to cellular immunity and the nature of T and B cell immunity is essential to realizing long-term protection against re-infection (9). It is not yet known how some people get re-infected despite having antibody titers. Can the presence of specific antibodies against other viral antigens compensate for the low titer of functional RBD specific antibodies? The answer is no. Experiments show that when the Ab-mediated complement deposition (ADCD) and Ab-dependent neutrophil phagocytosis (ADNP) tests were performed, virus neutralization was seen only in individuals with high IgG antibody titers against the RBD region. Therefore, it was concluded that only antibodies against RBD are neutralizing (10). However, it cannot be said that a high titer of anti-RBD antibody means high immunity because not all antibodies against RBD are neutralizing. Does it mean that there is no protection against re-infection if the antibodies lack good binding or function? We cannot say for sure because the role of the T cell, which acts as a strong immune responder to coronavirus disease 2019 (COVID-19), cannot be ignored. Suppose we measure the antibody titer in a number of volunteers at time T0 (test start time). Are only symptomatic people positive for neutralizing antibodies? According to an experiment conducted by YC Bartsch et al. (9) asymptomatic individuals also had specific antibodies against RBD with a specificity of over 99.5% by enzyme-linked immunosorbent assay (ELISA). This means that this antibody was present in both symptomatic and asymptomatic individuals, but its titer was higher in symptomatic individuals. After tracking subjects for antibody titers after a certain period of time, a small number of participants completely lost their antibody response, and in the remaining individuals, almost half of the subjects had decreased antibody titers and the other half had a dramatically increased antibody titers. This observation can be justified in two ways, first, that these people differed in the length of time they spent with the infection, and second, that people with elevated antibody titers may be re-exposed to the infection. Knowing this, it can be concluded that measuring the antibody titer after infection or vaccination will not give us accurate information about the level of protection against SARS-CoV-2 infection. Routine clinical laboratory methods such as ELISA will never be able to make sure that the antibodies produced in your body are neutralizing or not, because this requires specialized neutralizing tests. In addition, knowing the initial antibody titer, it is not easy to estimate that the rate of antibody reduction will be faster or slower. Therefore, models that predict immune responses to infection need to determine the link between the protection provided by expanding vaccines. Because in different studies, a single method has not been used to measure the neutralizing antibody titer, there is a need for data normalization methods to better compare the results. In addition, we suggest that in addition to measuring the neutralizing antibody titer, the responses of memory T and B cells, which are associated with high protection against SARS-CoV-2, be measured so that we can have a better prognosis for neutralization.

Next-Generation Sequencing (NGS) is a massive parallel sequencing technology that offers ultra-high throughput, scalability, and speed. This technology is used to determine the order of nucleotides throughout the genome or target regions of DNA or RNA. NGS has revolutionized the biological sciences, allowing laboratories to perform a variety of applications and study biological systems at a level that was not previously possible. Next generation sequencing technology is used in many laboratories around the world to study genetic structure, but so far this technology has rarely been used to diagnose infectious diseases. Most next generation sequencing methods are based on the chain termination process. Thus, with the addition of deoxy-nucleotide labeled with fluorescent ends the PCR reaction and sequence reading is performed (1). This technology makes it possible to map the entire genome at an affordable cost. Currently, the COVID-19 pandemic and SARS-CoV-2, the causative agent of this disease, which has many genomic changes and causes unusual occurrences in the clinic, has increasingly attracted the attention of scientists to higher levels of genetic studies (2, 3). The next generation sequencing technique is useful in obtaining essential information about a pathogen at the beginning of an infectious outbreak and can be used as a diagnostic method for COVID-19 infection (4) and can also be useful in accurately identifying concurrent infections in COVID-19 patients. The genomic epidemiology of SARS-CoV-2 has led to the identification of several mutations in the Wuhan SARS-CoV-2 strain. During the spring of 2020, a non-synonymous mutation leading to the replacement of the D614G in Spike protein dominated the reported sequences, resulting in a higher affinity for the ACE2 receptor, enhancing viral replication. Since the summer of 2020, the emergence of major viral variants has been observed (5). These variants have been shown to be responsible for successive epidemics in different geographical areas. Cases of re-infection with SARS-CoV-2 genotypes different from genotypes that first infected patients have also been reported (6). In order to track the evolution of the virus over time, many laboratories have examined the genotype of the virus. Laboratories equipped with the ability to sequence the entire genome have reported a large number of mutations that have increased over time. However, there are significant differences between countries and in some cases, there is no database of circulating viruses (7). Analysis of SARS-CoV-2 mutations is especially important when the epitopes involved in inducing host immune responses affect the host, as they may lead to immune escape, with potential implications for vaccine (and immunotherapy) efficacy. Such an event could be evidence of an increase in transmission associated with a series of performance-related mutations for a given geographic area. SARS-CoV-2 species are defined by a set of mutations associated with the pathogenesis of the virus, and many species are now closely monitored by the World Health Organization and other public health agencies around the world (6). Variants may be directly related to lineage because they spread under the same conditions, but some species do not (e.g. B.1.1.7 - E484K is a variant, but does not conform to a particular lineage because it reproduces independently many times). A number of variants of concern (VOCs) have been categorized by the WHO, which can be recognized as the alpha variant (B.1.1.7), which has 23 mutations (13 non-synonymous mutations, four deletions, and six synonymous mutations), and more transferability and increased related mortality; beta variants (B.1.351), Gamma, Delta, and Omicron BA-1 and BA-2 with 30 mutations in Spike mentioned. Some of these mutations have recently been linked to low vaccine efficacy. Mu and Lambda can also be mentioned as variants of interest (VOIs). Co-occurring bacterial and viral infections are common, and recognizing co-infection can be helpful in applying the appropriate treatment process to overcome the disease. The next generation sequencing involves a variety of techniques, including Illumina, Ion torrent, Target enrichment, Nanopore, Metagenomics Shotgun. These techniques are considered a new approach in the diagnosis of coronaviruses (1). But it is worth noting that each of them has different advantages in the diagnosis process. For example, Shotgun Metagenomics can confirm the presence of a new pathogen that is not known, and based on this, genotypic analyzes and analysis of different variants on the new pathogen can be performed (8). Target enrichment, on the other hand, evaluates the target sample by identifying the presence of coronavirus and other key respiratory viruses in a sample using the respiratory virus panel (9). Nanopore assay, meanwhile, is a method used to correct the error by reducing the error rate of each reading by comparing multiple genome versions combined into a single combination and by analyzing readings generated from positive and negative strands. Gives. Ion torrent is another sequencing method that is a kind of semiconductor sequencing technology and has a chip that has a sensitive pH sensor and identifies the hydrogen ions released during the alignment of nucleotides for the synthesis of the genomic chain. However, the mentioned methods are different from some other aspects, one of the parameters that are different in the expressed methods is the detection threshold, which is called (LOD) (10). In Illumina method, the detection limit parameter is less than 500 copies per milliliter, and in ion torrent and Nanopore assay, the detection limit is 20 copies and 10 copies per reaction, respectively. The COVID-19 epidemic has sparked unprecedented efforts for nations. The development of effective monitoring strategies is based on sequencing the genome of the causative agent with more than 100,000 complete genomes deposited in dedicated repositories such as EpiCov, and scientists have developed this data. Studies on the evolutionary dynamics of the virus, and the identification of clinically relevant types with different techniques and equipment have been performed, and based on this, it can be concluded that the methods have different diagnostic sensitivities that depend on the purpose of the study, researchers can choose one. Pay attention to the mentioned methods. Although NGS has not been completely successful in diagnosing congenital glycosylation disorders in the past, given the enormous potential of next-generation sequencing applications, it is likely that the various next-generation sequencing techniques mentioned will soon become the first diagnostic approach in clinical laboratories, and since pandemic, we expect the next generation sequencing technology could be a promising diagnostic approach.

Meningitis can quickly become a life-threatening sickness and therefore is considered a medical emergency. Viruses, after bacteria, are known as main pathogens involved in meningitis; therefore, we investigated the prevalence of viral meningitis worldwide and evaluated the clinical and preclinical features for rapid detection of viral meningitis. The results showed that the most prevalent viruses in viral meningitis are Enterovirus, Coxaci, Tick-borne encephalitis virus, Herpesviridae family; and the most prevalent viruses in aseptic meningitis are Echovirus, Enterovirus, Coxaci and HSV. The findings revealed differences in the prevalence of various viruses in these two types of meningitis, even though there was no significant difference in clinical manifestations between viral and bacterial meningitis. This indicates the importance of laboratory diagnostic methods for discriminating between these two types of meningitis.

Vaccination of children against hepatitis B virus (HBV) is the most effective strategy to prevent infections in their future life. However, the real response to HBV vaccination in infancy is still unclear. The aim of this study was to evaluate the status of immune response to HBV vaccine among children aged 8 to 18 months in east coast of the Caspian Sea, Bandar-e Turkmen, Golestan, Iran.
In this cross-sectional study, 565 children from Bandar-e Turkmen ranging from 8 to 18 months of age, vaccinated in a routine vaccination program were included. The serum samples were collected from all children and HBsAb titers were measured using ELISA.
Out of 565 children, 12 (2.12%) had anti-HBs titers <10 IU/L (non-responder) while 553 (97.88%) had anti-HBs titers >10 IU/L (responder) (p<0.05). Among these responder children, 92 (16.3%) had anti-HBs titers 10-100 IU/L (poor responder) and 461(81.6%) had anti-HBs titers >100 IU/L (good responder). The negative children were revaccinated (3-doses) and 11 of them became protected against HBV infection (anti-HBs titers >10 IU/L). Only 1 of the included children was non-responder, after routine vaccination and 3 doses revaccination.
The results of this study indicated that the HBV vaccination program in this region of Iran is effective and most of the children showed positive immune responses after three doses of vaccination. Importantly, revaccination of non-protected individuals is recommended

Vitamin A is fat-soluble compounds of retinoid derivate, consisting of retinol, retinal, and retinyl esters. Vitamin A also affects cell growth and differentiation, playing a critical role in the normal formation and function of the heart, lungs, kidneys, and other organs. According to the role of vitamin A in enhancing immune function, it is known as an anti-inflammation. Also, vitamin A supplementation by reducing morbidity and mortality in different infectious diseases, such as measles, diarrhoeal disease, measles-related pneumonia, human immunodeficiency virus infection, and malaria considered as a crucial factor against infection. So a deficiency in vitamin A can be a risk factor to human life, because of impairing the response to infection and significant risk of development of severe respiratory infections in infants and young children. In this paper, we will discuss the effects of vitamin A in modulating immune responses in viral infections and the direct effects of this vitamin on viral replication by comparing its role during different types of viral infections.

Following SARS-CoV-2 China epidemic in the December 2019, researches have attended to the genome of novel coronavirus. Hidden corners of SARS-CoV-2, maybe a shiny way to discover its pathogenicity and virulence. To design therapeutic agents, it is critical to map the complete repertoire of viral-translated proteins. Ribosome profiling is considered as a snapshot of all active ribosomes in a cell at a specific time point.

 The drug resistance mutations are key elements in the failure of long-term treatment of Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections. The mutation in the YMDD motif in the P gene of HBV is the most critical factor in antiviral drug (especially lamivudine) resistance. This study aimed to assess the YMDD motif and other polymerase gene mutations in individuals with HBV/HIV coinfection.

 All enrolled patients were under lamivudine treatment. Blood samples were collected from 37 HBV/HIV-positive patients, and DNA was extracted. The P gene was amplified by the PCR method with appropriate primers. The PCR products for detecting mutations in the P gene were sent to the Macrogen. To investigate the P gene mutations, the obtained sequences were compared with the polymerase gene of the HBV standard sequence in the GeneBank (accession number AB033559).

 The mean age of the patients was 34.1±5.7 years, of which 59.5% were male, and 40.5% were female. Of all patients, 56% were drug abusers, 35% had risky sexual behavior, 56% had prison history, and 33% had addicted wives. The 37 extracted samples were sequenced successfully. Among the studied samples (n =37), 28 patients had simultaneous mutations of YIDD and FLMAQ, 1 patient had YINN and FLIPH and 1 patient had YIDD and FSLAQ.

 In summary, drug-resistant variants were detectable in most coinfected patients with chronic Hepatitis B (CHB) and HIV. As a result of mutations, therapeutic strategies sometimes are not effective. Therefore, recognition and monitoring of drug resistance mutations are critical.

Summary Newcastle is one of the leading diseases among poultry. The viral agent of this disease is classified in the genus avulavirus of the paramyxovirus family. Since the disease has a harmful impact on poultry production, it is one of the main economic problems that can be studied by virology scientists. Even though, Newcastle disease virus (NDV) has been extensively studied in recent years, our information on immune responses to this virus remains incomplete. NDV is a zoonotic agent that can cause infection in humans. The common transmission route of NDV is through contact of contaminated fingers with the eyes after careless handling infectious poultry samples. Like all infectious diseases, vaccination can enhance NDV control. Today, there are three types of NDV vaccines, including live inactive and vector-based vaccines. Since NDV is an economical concern to governments, its problem must be solved. To find effective solutions to this problem, our knowledge about immune responses to ND has to be completed. In this review, we discussed some aspects of these responses.

Each year, many of Muslims including children and adolescents fast in Ramadan. This year, the month of Ramadan is in the period of the outbreak of COVID-19, and due to its spread, fighting this disease has brought about a new challenge for all Muslims in the world. Given the lack of studies on this issue, as well as the direct effect of fasting on the body and soul in the period of COVID-19 pandemic, this study intends to reflect the positive results of fasting in a mini-review. Therefore, online databases such as Web of Science, Scopus, Medline, EMBASE and Magiran were screened using the key words including: "Fasting", "Ramadan", "COVID-19", "Coronavirus", "Obesity", "Mental health", "Muslim" for the latest information. These keywords were searched from November 2001 to November 2020 in Persian and English languages. This study revealed that fasting by reducing obesity can help people to control their diabetes and cardiac diseases which are among the underlying diseases of COVID-19. In addition, fasting has an effective role in reducing violence and social problems. Interestingly, avoiding eating and drinking will reduce the contact of infected hands with mouth and reduces infection through swallowing.

The World Health Organization has identified COVID-19 as a public health priority of international concern. Due to lack of effective antiviral drugs or vaccines, it is necessary to discover effective treatment methods (1). Recently, there have been reports of SARS-CoV-2 infection indicating that the virus is found not only in the respiratory tract but also in the gastrointestinal tract. Although ACE2 has been shown to play a key role in protecting individuals against lung damage and intestinal epithelial inflammation, it is interesting to note that ACE2 protein expression decreases after infection with the virus (2). SARS-CoV-2, like SARS and Mers, is a beta-coronavirus. The SARS-CoV-2 genome has been sequenced, and according to the genomic sequence, SARS-CoV-2 has a 96% identity similar to bat coronavirus and 79.6% similar to SARS-CoV. Although there is no approved drug or vaccine for COVID-19, a number of clinical trials are ongoing (3). The development of new drugs is a time-consuming process and generally requires several years of clinical validation. In recent studies, viral proteins have been used as the target of molecular docking-based virtual screening. The predictions of these studies help us to select appropriate laboratory and clinical candidate drugs (4). On the other hand, the use of drugs that have been approved for some diseases and are safe for human consumption should be evaluated for effectiveness against the new disease. In life-threatening cases, such a drug strategy is highly desirable if there is an alternative drug or vaccine. However, clinical trials are needed to ensure that such treatment is appropriate (5).

The aim of this study was to review therapeutic candidates for the emerging COVID-19 disease. This study is a review study as a narrative review which has been obtained by searching in valid scientific databases such as Scopus, Google scholar, PubMed using the keywords virus, Corona, COVID-19, SARS-CoV-2, treatment of the latest information. Also, to receive the latest information from reputable sites in the field of health, such as the World Health Organization and the Center for Disease Control and Prevention have been used.

Recommended medications to combat viral infections are including of remdesivir, chlorquine or hydroxychloroquine, Methylprednisolone, combination of ritonavir and lupinavir, Favipiravir, fingolimod and bevacizumab. Remdesivir is a drug that is an adenosine analog used to inhibit the action of RNA polymerase and is used for Marburg and Ebola viruses (43). Chloroquine or hydroxychloroquine is effective in inhibiting endosomal acid fusion (33,34). Methylprednisolone is a synthetic corticosteroid that binds to nuclear receptors to reduce proinflammatory cytokines (26). The combination of ritonavir and lupinavir acts as a viral protease inhibitor (40). Favipiravir is a guanine analog and is an RNA-dependent RNA polymerase inhibitor (46). Fingolimod is an immunological modulator and is mostly used in patients with multiple sclerosis and by binding to sphingosine 1 phosphate receptors, it reduces the outflow of lymphocytes from the lymph nodes (30). Bevacizumab acts against vascular endothelial growth factor (VEGF) to prevent hypoxia and inflammation caused by this factor in the respiratory epithelium (21). In addition to the above drugs, many drugs are currently being studied in different countries to confirm their effectiveness in treating COVID-19, which are listed in Table 3.

Due to the time-consuming nature of the development and registration of antiviral drugs, available treatments for other diseases may be the fastest emerging treatment option for infectious diseases. Broad-spectrum drugs such as bevacizumab, methylprednisolone, fingolimod, flupinavir, ritonavir, chloroquine phosphate, remedicivir, and favipiravir are currently being studied in various clinical trials as candidates for treatment. Therefore, it can be concluded that the use of all these drugs, in turn, can have a significant effectiveness in combating this disease. Of course, it should be noted that none of these drugs is the definitive and specific drug COVID19, and efforts to find a specific drug for this disease should continue until the definitive drug is available.

Helicobacter pylori (H. pylori) is a gram-negative, microaerophilic, spiral-shaped flagellated bacterium that is urease, catalase and oxidase positive. One of its pathogenicity factors is the iceA gene. H. pylori has recently been recognized as a genetic indicator for the development and evolution of duodenal ulcer disease in the East. This study aimed to determine the presence of this bacterium in gingival plaques in non-endocrine patients in Bojnourd city, and the polymerase chain reaction technique examined the percentage of iceA gene.

A total of 100 samples of dental plaque were taken and transferred to a tube that has been physiologically placed. After DNA extraction, primer design was performed, and then the polymerase chain reaction was performed for the whole sample.

Of 100 samples examined in this study, two samples of H. pylori were positive (2%), and the frequency of the iceA gene of two samples was positive (100%).

In the Bojnord city, the frequency of iceA gene in people is high, and the frequency of H. pylori in tooth plaques is low. Also, iceA gene can be considered as an indicator for predicting the contamination and risk of H. pylori infection in the region. To confirm the results, more molecular studies are required in other populations.

Bacteriophages are viruses that can kill bacteria with the least adverse effect on human or animal host cells). Phage therapy is the use of bacterial viruses (phage) to treat bacterial infections, a medical intervention that has long been abandoned in the West but is now experiencing resurgence. At present, therapeutic phages are often selected based on limited criteria, which are sometimes simple as the ability to bind to pathogenic bacteria. Therefore, the use of therapeutic methods and antibacterial properties of phages is known as phage therapy, especially in clinical or veterinary fields. More widely, phages have been used as biological control agents to reduce the amount of bacteria in food. In addition, modified phages can be used as tools of transmitting DNA, protein or medicine. Various problems in the treatment of many life-threatening bacterial infections have led scientists to review phages. Numerous studies on the use of phage in vitro, in laboratory animals, and in humans have been performed in the United States and Europe. For this reason, phages can be used alone or in combination with antibiotics to treat bacterial infections. This article reviews a number of aspects of the use of phages and their products in the medical and especially antibacterial fields.

In this review study, all studies to date have been reviewed and searched through databases such as Irandoc, Scopus, Google scholar, PubMed and other reputable scientific databases with keyword searches such as bacteriophage, phage therapy, Biological treatment, infection, bacterial and the latest information has been obtained.

Due to the high prevalence of antibiotic resistance in different bacterial infections, the use of bacteriophages is one of the best options for the treatment of bacterial diseases. Therefore, different aspects of therapeutic use in patients at different levels have been studied and the advantages of using phages over antibiotics have been determined in all cases. Bacteriophages invade biofilms and in these cases they can be an alternative treatment to antibiotics. Most of studies are on using phages for the topical treatment of bacterial skin infections. Some chronic skin infections, such as acne, may require long-term antibiotic treatment, although they are not life-threatening. The immunosuppressive activity of pure bacteriophages may be an argument for the safety of phage therapy, especially in allograft recipients. Excessive levels of immunosuppression due to the concomitant activity of immunosuppressive drugs and phages can increase the risk of other infections. Obviously, cancer patients and people with immunodeficiency will be at greater risk for infections following phage therapy. The use of bacteriophages, in addition to its benefits for the treatment of bacterial infections, has disadvantages such as the narrow range of bacterial hosts for phage, insufficient purity of phage, difficulty in removing integrase genes, phage resistance, Antibiotic resistance, decreased phage function due to neutralizing immune system involvement, pre-prepared phage instability, lack of understanding of phage heterogeneity and function, exaggerated claims about the effectiveness of commercial phage preparation, and Lack of scientific evidence for the effectiveness of phage treatment.

Despite the apparent need for new and safe antibacterial drugs, the use of phages as biological therapies by most physicians has not yet been addressed, and this is probably due to a lack of familiarity with phage therapy, as well as another reason for the lack of regulatory approval. We believe that, given the widespread crisis of antibiotics, this approach requires serious attention. Because despite the many restrictions on the use of phages, these biological tools still have many unique applications in medicine.