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1.
Iran J Med Sci ; 47(1): 1, 2022 01.
Article in English | MEDLINE | ID: covidwho-1761633

Subject(s)
Medicine , Publishing , Iran
2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-321139

ABSTRACT

As the outbreak of COVID-19 has accelerated, an urgent need for finding strategies to combat the virus is growing. Thus, gaining more knowledge on the pathogenicity mechanisms of SARS-CoV-2, the causing agent of COVID-19, and its interaction with the immune system is of utmost importance. Although this novel virus is not well known yet, its structural and genetic similarity with SARS-CoV as well as the comparable pattern of age-mortality relations suggest that the previous findings on SARS can be applicable for COVID-19. Therefore, a systems biology study was conducted to investigate the most important signaling pathways activated by the virus. The results were then validated through a literature review on COVID-19 and the other closely related viruses, SARS and MERS. Interferons have shown to play a crucial role in the defense against coronavirus diseases. CoV can impede the interferon induction in humans. Moreover, STAT1, a key protein in the interferon-mediated immune response, is antagonized by the virus. This could explain the increased response threshold of immune cells to IFNs during CoV infections. A vivid correlation between the innate immune response threshold and the fatality rates in COVID-19 can be found. Differences in the dynamics of the interferon-related innate immune responses in children, adults, and elderly may explain the reported fatality rates. The increased mortality rates in the elderly can be explained by the higher threshold of interferon-mediated immune responses. Earlier induction of interferons in children and their less developed immune system could contribute to their near to zero fatality rate. Administration of interferon-inducing agents, such as poly (ICLC), could reduce the mortality of SARS at the very early stages of the disease. Interferon-γcombination with an interferon-I might induce synergistic effects and maximize the benefits. However, in-depth research is needed to validate it and determine the optimum dosage and timing to prevent unwanted results. Such interventions can act as a double-edged sword and aid the imbalance of the immune reactions, which may occur at the later stages of the disease. With the advancement of the disease and the virus overload, the responses would shift toward immnopathogenic over-reactions and probably cytokine storm. Moderating the activity of the immune system and supportive care in such conditions might be the optimum approach.

3.
Comput Math Methods Med ; 2022: 9735626, 2022.
Article in English | MEDLINE | ID: covidwho-1677416

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was characterized as a pandemic by the World Health Organization (WHO) in Dec. 2019. SARS-CoV-2 binds to the cell membrane through spike proteins on its surface and infects the cell. Furin, a host-cell enzyme, possesses a binding site for the spike protein. Thus, molecules that block furin could potentially be a therapeutic solution. Defensins are antimicrobial peptides that can hypothetically inhibit furin because of their arginine-rich structure. Theta-defensins, a subclass of defensins, have attracted attention as drug candidates due to their small size, unique structure, and involvement in several defense mechanisms. Theta-defensins could be a potential treatment for COVID-19 through furin inhibition and an anti-inflammatory mechanism. Note that inflammatory events are a significant and deadly condition that could happen at the later stages of COVID-19 infection. Here, the potential of theta-defensins against SARS-CoV-2 infection was investigated through in silico approaches. Based on docking analysis results, theta-defensins can function as furin inhibitors. Additionally, a novel candidate peptide against COVID-19 with optimal properties regarding antigenicity, stability, electrostatic potential, and binding strength was proposed. Further in vitro/in vivo investigations could verify the efficiency of the designed novel peptide.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/metabolism , Defensins/pharmacology , Drug Design , Furin/antagonists & inhibitors , Animals , COVID-19/drug therapy , Catalytic Domain , Cell Membrane/virology , Computer Simulation , Data Mining , Furin/chemistry , Humans , Inflammation , Models, Molecular , Molecular Docking Simulation , Peptides/chemistry , Software , Spike Glycoprotein, Coronavirus , Static Electricity
4.
Sci Rep ; 11(1): 23622, 2021 12 08.
Article in English | MEDLINE | ID: covidwho-1559938

ABSTRACT

Spike glycoprotein (Sgp) is liable for binding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to the host receptors. Since Sgp is the main target for vaccine and drug designing, elucidating its mutation pattern could help in this regard. This study is aimed at investigating the correspondence of specific residues to the SgpSARS-CoV-2 functionality by explorative interpretation of sequence alignments. Centrality analysis of the Sgp dissects the importance of these residues in the interaction network of the RBD-ACE2 (receptor-binding domain) complex and furin cleavage site. Correspondence of RBD to threonine500 and asparagine501 and furin cleavage site to glutamine675, glutamine677, threonine678, and alanine684 was observed; all residues are exactly located at the interaction interfaces. The harmonious location of residues dictates the RBD binding property and the flexibility, hydrophobicity, and accessibility of the furin cleavage site. These species-specific residues can be assumed as real targets of evolution, while other substitutions tend to support them. Moreover, all these residues are parts of experimentally identified epitopes. Therefore, their substitution may affect vaccine efficacy. Higher rate of RBD maintenance than furin cleavage site was predicted. The accumulation of substitutions reinforces the probability of the multi-host circulation of the virus and emphasizes the enduring evolutionary events.


Subject(s)
SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/genetics , Amino Acid Sequence , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/metabolism , Binding Sites , COVID-19/pathology , COVID-19/virology , Cluster Analysis , Humans , Markov Chains , Mutation , Protein Binding , Protein Domains/genetics , SARS-CoV-2/isolation & purification , Sequence Alignment , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism
5.
Eur J Pharm Sci ; 169: 106094, 2022 Feb 01.
Article in English | MEDLINE | ID: covidwho-1558464

ABSTRACT

Viral infections are a great threat to human health. Currently, there are no effective vaccines and antiviral drugs against the majority of viral diseases, suggesting the need to develop novel and effective antiviral agents. Since the intracellular delivery of antiviral agents, particularly the impermeable molecules, such as peptides, proteins, and nucleic acids, are essential to exert their therapeutic effects, using a delivery system is highly required. Among various delivery systems, cell-penetrating peptides (CPPs), a group of short peptides with the unique ability of crossing cell membrane, offer great potential for the intracellular delivery of various biologically active cargoes. The results of numerous in vitro and in vivo studies with CPP conjugates demonstrate their promise as therapeutic agents in various medical fields including antiviral therapy. The CPP-mediated delivery of various antiviral agents including peptides, proteins, nucleic acids, and nanocarriers have been associated with therapeutic efficacy both in vitro and in vivo. This review describes various aspects of viruses including their biology, pathogenesis, and therapy and briefly discusses the concept of CPP and its potential in drug delivery. Particularly, it will highlight a variety of CPP applications in the management of viral infections.


Subject(s)
Cell-Penetrating Peptides , Nucleic Acids , Vaccines , Antiviral Agents , Drug Delivery Systems , Humans
7.
Int Immunopharmacol ; 99: 108021, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1380684

ABSTRACT

Since the beginning of vaccination programs against COVID-19 in different countries, several populations such as patients with specific immunological conditions have been considered as the priorities for immunization. In this regard, patients with autoimmune diseases or those receiving immunosuppressive agents and anti-cancer therapies, need special attention. However, no confirmed data is presently available regarding COVID-19 vaccines in these populations due to exclusion from the conducted clinical trials. Given the probable suppression or over-activation of the immune system in such patients, reaching a consensus for their vaccination is critical, besides gathering data and conducting trials, which could probably clarify this matter in the future. In this review, besides a brief on the available COVID-19 vaccines, considerations and available knowledge about administering similar vaccines in patients with cancer, hematopoietic stem cell transplantation, solid organ transplantation, multiple sclerosis (MS), inflammatory bowel disease (IBD), and rheumatologic and dermatologic autoimmune disorders are summarized to help in decision making. As discussed, live-attenuated viruses, which should be avoided in these groups, are not employed in the present COVID-19 vaccines. Thus, the main concern regarding efficacy could be met using a potent COVID-19 vaccine. Moreover, the vaccination timing for maximum efficacy could be decided according to the patient's condition, indicated medications, and the guides provided here. Post-vaccination monitoring is also advised to ensure an adequate immune response. Further studies in this area are urgently warranted.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Immunocompromised Host/immunology , Humans , Immune System Diseases/immunology , Immunization , SARS-CoV-2 , Vaccination
8.
Biologia (Bratisl) ; 76(11): 3465-3476, 2021.
Article in English | MEDLINE | ID: covidwho-1361327

ABSTRACT

The ongoing global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has prompted worldwide vaccine development. Several vaccines have been authorized by WHO, FDA, or MOH of different countries. However, issues such as need for cold chain, price, and most importantly access problems have limited vaccine usage in some nations especially developing countries. Moreover, the vast global demand justifies further attempts for vaccine development. Multi-epitope polypeptide vaccines enjoy several key features including safety and lower production and transfer costs and could be designed by in silico tools. Spike protein (S), membrane protein (M), and nucleocapsid protein (N), the three major structural proteins of SARS-CoV-2, are ideal candidates for epitope selection. ORF3a (open reading frame3a), a transmembrane protein with pro-apoptotic functions, could be another proper target. Thus, a novel multi-epitope vaccine against SARS-CoV-2 was designed using these four proteins and LL37, a TLR3 agonist adjuvant, through different immunoinformatics and bioinformatics tools. The proposed multi-epitope vaccine is expected to induce robust humoral and cellular immune responses against SARS-CoV-2 with a population coverage of 76.92 % due to containing different immunodominant epitopes and LL37 adjuvant. Selecting epitopes derived from one functional and three structural proteins suggests the protective ability of the vaccine irrespective of probable virus mutations. The computationally observed proper interaction of LL37 with TLR3 implies its ability to induce immune responses effectively. Besides, it showed acceptable structural and physicochemical properties. The in-silico cloning results predicted its high efficiency production in Escherichia coli. Future experimental studies could further confirm its immunological efficacy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11756-021-00866-y.

9.
RSC Adv ; 11(38): 23815-23824, 2021 Jul 01.
Article in English | MEDLINE | ID: covidwho-1323767

ABSTRACT

Entrance of coronavirus into cells happens through the spike proteins on the virus surface, for which the spike protein should be cleaved into S1 and S2 domains. This cleavage is mediated by furin, a member of the proprotein convertases family, which can specifically cleave Arg-X-X-Arg↓ sites of the substrates. Here, folate (folic acid), a water-soluble B vitamin, is introduced for the inhibition of furin activity. Therefore, molecular insight into the prevention of furin activity in the presence of folic acid derivatives is presented. To this aim, molecular docking, molecular dynamics (MD) simulations, and binding free energy calculations were performed to clarify the inhibitory mechanism of these compounds. In this regard, molecular docking studies were conducted to probe the furin binding sites of folic acid derivatives. The MD simulation results indicated that these drugs can efficiently bind to the furin active site. While the folic acid molecule tended to be positioned slightly towards the Glu271, Tyr313, Ala532, Gln488, and Asp530 amino acids of furin at short and long ranges, the folinic acid molecule interacted with Glu271, Ser311, Arg490, Gln488, and Lys499 amino acids. Consequently, binding free energy calculations illustrated that folic acid (-27.90 kcal mol-1) has better binding in comparison with folinic acid (-12.84 kcal mol-1).

11.
Hum Vaccin Immunother ; 17(6): 1650-1661, 2021 06 03.
Article in English | MEDLINE | ID: covidwho-1214420

ABSTRACT

No proven remedy is identified for COVID-19 yet. SARS-CoV-2, the viral agent, is recognized by some endosomal and cytosolic receptors following cell entry, entailing innate and adaptive immunity stimulation, notably through interferon induction. Impairment in immunity activation in some patients, mostly elderlies, leads to high mortalities; thus, promoting immune responses may help. BCG vaccine is under investigation to prevent COVID-19 due to its non-specific effects on the immune system. However, other complementary immune-induction methods at early stages of the disease may be needed. Here, the potentially preventive immunologic effects of BCG and influenza vaccination are compared with the immune response defects caused by aging and COVID-19. BCG co-administration with interferon-α/-ß, or influenza vaccine is suggested to overcome its shortcomings in interferon signaling against COVID-19. However, further studies are highly recommended to assess the outcomes of such interventions considering their probable adverse effects especially augmented innate immune responses and overproduction of proinflammatory mediators.


Subject(s)
BCG Vaccine/therapeutic use , COVID-19/prevention & control , Influenza Vaccines/therapeutic use , Clinical Trials as Topic , Humans , Immunity, Innate , Interferons/therapeutic use , Pandemics , Prospective Studies
12.
Recent Pat Biotechnol ; 15(2): 112-136, 2021 Oct 04.
Article in English | MEDLINE | ID: covidwho-1194530

ABSTRACT

BACKGROUND: Viral respiratory infections could result in perturbation of the gut microbiota due to a probable cross-talk between lungs and gut microbiota. This can affect pulmonary health and the gastrointestinal system. OBJECTIVE: This review aimed to discuss the impact of probiotics/prebiotics and supplements on the prevention and treatment of respiratory infections, especially emerging pathogens. METHODS: The data were searched in PubMed, Scopus, Google Scholar, Google Patents, and The Lens-Patent using keywords of probiotics and viral respiratory infections in the title, abstract, and keywords. RESULTS: Probiotics consumption could decrease the susceptibility to viral respiratory infections, such as COVID-19 and simultaneously enhance vaccine efficiency in infectious disease prevention through the immune system enhancement. Probiotics improve the gut microbiota and the immune system via regulating the innate system response and production of anti-inflammatory cytokines. Moreover, treatment with probiotics contributes to intestinal homeostasis restitution under antibiotic pressure and decreasing the risk of secondary infections due to viral respiratory infections. Probiotics present varied performances in different conditions; thus, promoting their efficacy through combining with supplements (prebiotics, postbiotics, nutraceuticals, berberine, curcumin, lactoferrin, minerals, and vitamins) is important. Several supplements reported to enhance the probiotics' efficacy and their mechanisms as well as probiotics- related patents are summarized in this review. Using nanotechnology and microencapsulation techniques can also improve probiotics' efficiency. CONCLUSION: Given the global challenge of COVID-19, probiotic/prebiotic and following nutritional guidelines should be regarded seriously. Additionally, their role as an adjuvant in vaccination for immune response augmentation needs attention.


Subject(s)
Prebiotics , Probiotics , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/prevention & control , Adjuvants, Immunologic , COVID-19/drug therapy , COVID-19/immunology , COVID-19/microbiology , COVID-19/prevention & control , Dietary Supplements , Gastrointestinal Microbiome , Humans , Respiratory Tract Infections/immunology , Respiratory Tract Infections/microbiology , SARS-CoV-2
14.
Int Immunopharmacol ; 91: 107245, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-950776

ABSTRACT

Coronavirus disease 2019 (COVID-19) is an infective disease generated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Given the pandemic urgency and lack of an effective cure for this disease, drug repurposing could open the way for finding a solution. Lots of investigations are ongoing to test the compounds already identified as antivirals. On the other hand, induction of type I interferons are found to play an important role in the generation of immune responses against SARS-CoV-2. Therefore, it was opined that the antivirals capable of triggering the interferons and their signaling pathway, could rationally be beneficial for treating COVID-19. On this basis, using a database of antivirals, called drugvirus, some antiviral agents were derived, followed by searches on their relevance to interferon induction. The examined list included drugs from different categories such as antibiotics, immunosuppressants, anti-cancers, non-steroidal anti-inflammatory drugs (NSAID), calcium channel blocker compounds, and some others. The results as briefed here, could help in finding potential drug candidates for COVID-19 treatment. However, their advantages and risks should be taken into account through precise studies, considering a systemic approach. Even though the adverse effects of some of these drugs may overweight their benefits, considering their mechanisms and structures may give a clue for designing novel drugs in the future. Furthermore, the antiviral effect and IFN-modifying mechanisms possessed by some of these drugs might lead to a synergistic effect against SARS-CoV-2, which deserve to be evaluated in further investigations.


Subject(s)
Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Interferon Type I/pharmacology , Interferon Type I/therapeutic use , SARS-CoV-2/drug effects , Animals , COVID-19/virology , Humans , Pandemics/prevention & control
15.
Iran J Med Sci ; 45(6): 403-404, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-946575
16.
Int Immunopharmacol ; 88: 106924, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-725252

ABSTRACT

COVID-19, the disease induced by the recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has imposed an unpredictable burden on the world. Drug repurposing has been employed to rapidly find a cure; but despite great efforts, no drug or vaccine is presently available for treating or prevention of COVID-19. Apart from antivirals, immunotherapeutic strategies are suggested considering the role of the immune response as the host defense against the virus, and the fact that SARS-CoV-2 suppresses interferon induction as an immune evasion strategy. Active immunization through vaccines, interferon administration, passive immunotherapy by convalescent plasma or synthesized monoclonal and polyclonal antibodies, as well as immunomodulatory drugs, are different immunotherapeutic approaches that will be mentioned in this review. The focus would be on passive immunotherapeutic interventions. Interferons might be helpful in some stages. Vaccine development has been followed with unprecedented speed. Some of these vaccines have been advanced to human clinical trials. Convalescent plasma therapy is already practiced in many countries to help save the lives of severely ill patients. Different antibodies that target various steps of SARS-CoV-2 pathogenesis or the associated immune responses are also proposed. For treating the cytokine storm induced at a late stage of the disease in some patients, immune modulation through JAK inhibitors, corticosteroids, and some other cognate classes are evaluated. Given the changing pattern of cytokine induction and immune responses throughout the COVID-19 disease course, different adapted approaches are needed to help patients. Gaining more knowledge about the detailed pathogenesis of SARS-CoV-2, its interplay with the immune system, and viral-mediated responses are crucial to identify efficient preventive and therapeutic approaches. A systemic approach seems essential in this regard.


Subject(s)
Coronavirus Infections/drug therapy , Immunotherapy/methods , Pneumonia, Viral/drug therapy , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/therapeutic use , Antibodies, Viral/blood , Betacoronavirus , COVID-19 , COVID-19 Vaccines , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Coronavirus Infections/therapy , Humans , Immunization, Passive , Interferons/administration & dosage , Interferons/therapeutic use , Pandemics/prevention & control , Pneumonia, Viral/immunology , Pneumonia, Viral/prevention & control , SARS-CoV-2 , Treatment Outcome , Viral Vaccines/administration & dosage , Viral Vaccines/immunology
17.
Iran J Med Sci ; 45(4): 231-232, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-661562
18.
Iran J Med Sci ; 45(3): 155-156, 2020 May.
Article in English | MEDLINE | ID: covidwho-208508
19.
Iran J Med Sci ; 45(2): 81-82, 2020 Mar.
Article in English | MEDLINE | ID: covidwho-18521
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