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Virology: Current Research

ISSN: 2736-657X

Open Access

Current Issue

Volume 5, Issue 1 (2021)

    Research Pages: 1 - 6

    Direct ACE2- Spike RBD Binding Disruption With Small Molecules: A Strategy For COVID-19 Treatment

    Bartlomiej P. Przychodzen*, Sandra P. Smieszek, Christos M. Polymeropoulos, Vasilios M. Polymeropoulos and Mihael H. Polymeropoulos

    ACE2 is a key receptor for SARS-CoV-2 cell entry. Binding of SARS-Cov-2 to ACE2 involves the viral Spike protein. The molecular interaction between ACE2 and Spike has been resolved. Interfering with this interaction might be used in treating patients with COVID-19. Inhibition of this interaction can be attained via multiple routes: here we focus on identifying small molecules that would prevent the interaction. Specifically we focus on small molecules and peptides that have the capacity to effectively bind the ACE2: RBD contact domain to prevent and reduce SARS-CoV-2 entry into the cell. We aim to identify molecules that prevent the docking of viral spike protein (mediated by RBD) onto cells expressing ACE2, without inhibiting the activity of ACE2. We utilize the most recent ACE2-RBD crystallography resolved model (PDB-ID: 6LZG). Based on animal susceptibility data we narrowed down our interest to the location of amino acid 34 (Histidine) located on ACE2. We performed an in silico screen of a chemical library of compounds with several thousand small molecules including FDA approved compounds. All compounds were tested for binding to the proximal binding site located close to histidine 34 on ACE2. We report a list of four potential small molecules that potentially have the capacity to bind target residue: AY-NH2, a selective PAR4 receptor agonist peptide (CAS number: 352017-71-1), NAD+ (CAS number: 53- 84-9), Reproterol, a short-acting β2 adrenoreceptor agonist used in the treatment of asthma (CAS number: 54063-54-6), and Thymopentin, a synthetic immune- stimulant which enhances production of thymic T cells (CAS number: 69558-55-0). The focus is on a High Throughput Screen Assay (HTSA), or in silico screen, delineating small molecules that are selectively binding/masking the crucial interface residue on ACE2 at His34. Consequently, inhibiting SARS-CoV-2 binding to host ACE2 and viral entry is a potent strategy to reduce cellular entry of the virus. We suggest that this anti-viral nature of this interaction is a viable strategy for COVID19 whereas the small molecules including peptides warrant further in vitro screens.

    Research Article Pages: 1 - 6

    In silico Docking for Inhibition Neuropilin-1 (Sars-Cov-2 Receptor) by Some Natural Compound and Approved Drugs

    Mohamed Gomaa Seadawy*, Mohamed Shamel Eldesoky, Aya Ahmed and Abdel Rahman Nabwi Zekri

    Background: Neuropilin-1 (NRP-1) is a multifunctional transmembrane receptor for ligands that affect developmental axonal growth and angiogenesis. Beside its role in cancer, NRP-1 is a reported entrance for several viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of coronavirus disease 2019 (COVID-19).

    Methods: We made Insilco docking between the spike protein and Neuropilin-1 using Cluspro 2.0 software. Therefore, Neuropilin-1 becomes host factor for SARSCoV- 2 infection. Then by using molecular docking, we test nine compounds against Neuropilin-1 for its inhibition.

    Results and Conclusion: Our study revealed that some drugs and natural compounds success in inhibition of binding between the virus and its new receptor with Insilco docking data.

    Mini Review Pages: 1 - 3

    Establishing PCR Testing in Nepal for COVID-19: Challenges and Opportunities

    Ram Bahadur Khadka

    Polymerase Chain Reaction (PCR) invented by Kary Mullis (1983), has become the centrepiece of molecular detection of various infectious diseases including coronavirus disease 2019 (COVID-19). Many developing countries like Nepal faces various challenges and grab many future opportunities during and after establishment of molecular PCR laboratories throughout the country. This viewpoint describes the involvement of laboratory employees, development and adoption of new protocols or framework, deliberate partnership with national and international community is very efficient for the establishment of PCR laboratories. Beside this, continued alliance and nation leadership is crucial to generate a unified and sustainable PCR laboratory network in the country like Nepal. In future the established PCR laboratories can be utilized for the diagnosis of others pandemic diseases and can be used for multipurpose like in verification of infectious diseases; Oncology; Blood test; Genetic testing.

    Research Article Pages: 1 - 6

    Exploring Indian Spices as Promising Antimicrobial Agents

    Kirti Garg and Astha Giri

    Infectious diseases caused by pathogens, and food contamination caused by microorganisms, are compromising human health. The efficacies of antimicrobial agents and antibiotics, which are currently being used, have been weakened by microbial resistance, while antibiotic toxicity is a known challenge. This arises the need of natural antimicrobial agents. Spices and herbs have been long used for centuries, to enhance flavour and aroma of food, and for their antimicrobial and antioxidant activities. In this study, antimicrobial activity of aqueous and ethanolic extracts of five Indian spices i.e., Black pepper, Carom, Cinnamon, Clove and Cumin, was explored against Escherichia coli and Staphylococcus aureus, by agar dilution method and disk diffusion method. For agar dilution, aqueous and ethanolic extracts, with concentrations ranging from 0.5 mg/ml-8 mg/ml, were used. Whereas for disc diffusion method, varying concentrations of the ethanolic extracts (50%, 75% and 100%) were used. The results indicated an inhibitory effect on the growth of the microbes when using higher concentration of the extract. Clove’s bud showed the best antimicrobial effect amongst all the tested spices, having Minimum Inhibitory Concentration (MIC) less than 0.5 mg/ml for aqueous extract and 6 mg/ml for ethanolic extract against both bacteria. Amongst the tested spice extracts, Clove also had the biggest zone of inhibition i.e., 21 mm, against E. coli when using 50% ethanolic extract, while Black pepper had a zone of inhibition of 20 mm against S. aureus when using 100% ethanolic extract. It was also noted that the spice extracts, in general, were more effective against S. aureus than E. coli. Therefore, spices and particularly Clove and Black pepper extracts have great potential to be further tested and developed as novel safe antimicrobial agents

    Volume 5, Issue 2 (2021)

      Research Article Pages: 1 - 5

      Molecular Docking Study of Novel COVID-19 Protease with Low-Risk Terpenoids Compounds of Plants

      Neda Shaghaghi

      Background: Due to the reported high ability of virulence of COVID-19 in recent months, several studies have been conducted to discover and introduce COVID-19 antiviral drugs. The results of numerous studies have shown that protease inhibitors and compounds, which make up the major part of plant derivatives, especially terpenoids, can therefore be very effective in controlling virus-induced infection. The aim of this research is the bioinformatical study of COVID-19 inhibition by terpenoids of plant origin.

      Materials and methods: This is a descriptive-analytic study. In the present study, the structure of Terpene compounds were received from the databases such as PubChem and COVID-19 proteases were received Protein Data Bank (PDB). After that, molecular docking was performed by MVD (molegro virtual docker) software.

       Results: The results are identified to have inhibitory activities against novel COVID-19 protease. Of these compounds, Ginkgolide A has a stronger bond and high affinity with protease. The amount of connecting energy from high to less in order Ginkgolide A> DiThymoquinone>Noscapine>Salvinorin A>Forscolin>Bilobalide>Citral>Beta Selinene>Menthol. All of these compounds were linked to the intermediate flap that the software had predicted, and all of them were binded to 8 residues, and a total of 19 residues were binded.

      Conclusion: Finally, with due attention to the high effectiveness function of terpenoids, we can conclude that these compounds may be considered as effective COVID-19 antiprotease drugs. Also, due to the formation of blood clots in coronavirus infection, a number of these compounds, in addition to antiviral activity, have an effect on inhibiting coagulation.

      Research Article Pages: 1 - 6

      Investigation of Cepharanthine Binding with Viral Proteins Reveal its Potential Targets against Coronavirus

      Donghui Huo, Wenlin An, Huan Xu, Aixia Yan and Yigang Tong

      The outbreak of Corona Virus Disease 2019 (COVID-19) caused by SARS-CoV-2 is becoming a worldwide problem. We previously reported that cepharanthine (CEP) demonstrated strong anti-coronavirus effects, however, the mechanism underlying CEP’s anti-coronavirus effects remains unknown. We herein performed Surface Plasmon Resonance (SPR) to investigate the biological influence of CEP on different proteins of SARS-CoV-2. Meanwhile, molecular docking study was used to screen the potential binding sites of CEP on the virus. The binding of CEP to the nsp13 helicase with a Kd of 3.806*10-6 M shows that helicase is a relatively strong possible target of CEP. Besides, CEP could bind to the viral main proteinase (3CLpro) that contributes to the intervention of polypeptide cleavage. We also compared the potential binding pockets and binding affinity on viral spike proteins (S1 and S2 subunits) at both open and closed states. Our study revealed that CEP exerts its anti-coronavirus effects at viral genomic RNA replication, transcription, translation and viral invasion levels, providing a theoretical basis for the development of CEP as a promising anti-coronavirus drug.

      Editorial Pages: 1 - 1

      WHO Renews Backing for Astrazeneca COVID

      George Sourvinos

      The World Health Organization gave sturdy backing to the AstraZeneca COVID-19 jab on Friday, urging countries to take care of the roll-out once reviewing reports of blood clots. Many European countries resumed AstraZeneca vaccinations on Friday once the European Medical Agency (EMA) likewise gave their inexperienced lightweight. "We perceive that individuals could have had considerations regarding the security of the Oxford-AstraZeneca immunogen. The question with any pharmaceutical or immunogen is whether or not the chance of taking it's bigger or but the chance of the malady it's meant to stop or treat. There's no question: COVID-19 could be a deadly malady and therefore the Oxford-AstraZeneca immunogen will forestall it. The obtainable information don't recommend any overall increase in natural action conditions following administration of the Oxford-AstraZeneca COVID-19 immunogen. We tend to urge countries to continue victimization this necessary immunogen. 'Tremendous potential' The WHO's world consultatory Committee on immunogen Safety (GACVS) met nearly associated It reviewed obtainable info and information on thromboembolic events (blood clots) and thrombopenia (low platelets) once vaccination with an AstraZeneca COVID-19 shot.

      Research Article Pages: 1 - 5

      Potential Docking Affinity of Three Approved Drugs Against SARS-CoV-2 for COVID-19 Treatment

      Venkata Sambasiva Rao Rachakulla and Hemanjali Devi Rachakulla

      Objectives: As the COVID-19 is rapidly spreading entire world and even though vaccines are distributing on emergency basis. There are enormous delays in supply chain due to huge gap between demand and production and also time factor for different phases of vaccination in the entire world. There is urgent need of alternate effective drug candidates from among the drugs already approved by FDA.

      Methods: We have studied the virtual interaction of crystal data structures of protein downloaded from protein data bank (PDB ID 7BRP) docked with corticosteroid drug candidates approved by FDA for other medical purposes which have less side effects. The results are analyzed in contrast some drugs candidates currently using for the treatment of COVID-19.

      Results: The binding energies in kilocalories/mole obtained from the docking of 7BRP protease with ligands under investigation Betamethasone Phosphate (-6.9), Fluticasone (-6.1) and Dexamethasone (-5.9) and also with currently using drug candidates Remdesivir (-6.5), Lopinavir (-6.0), Baceprivir (-5.7), Rabavirin (-6), Ritinovir (-5.3), Hydroxyquinoline (-5.0), Chloroquine (-4.7), Oseltamivir (-4.6), Favipiravir (-3.9).

      Discussion: The docking results suggest a higher binding affinity of the drug molecules under investigation against SARS-CoV-2 in contrast with other drug candidates currently being used for the treatment of COVID-19. We have analyzed bond interactions of protein-ligand from images in 10 modes of investigated drugs in contrast with Remdesivir and discussed the advantages of inhalation methods of drug fluticasone.

      Conclusion: From this study, it can be suggested that these carticosteroid drugs are promising candidates for antiviral treatment with high potential to fight against SARS-CoV-2 strain which needs further clinical studies. Especially, fluticasone an inhaler drug promising candidate which targets the infected lungs by COVID-1

      Research Article Pages: 1 - 7

      COVID-19 Pandemic and Bangladesh: A Review

      Mohammed Kamruzzaman

      Bangladesh, a developing country in the world. Like the other countries in the world it also hit by COVID-19 pandemic. This review article particularly analyzed some issues (e.g. Government measures, Economy, Mental health, Social issues and Vaccine) of Bangladesh related to COVID-19. Based on the published articles, news from print and electronic media, websites of different government and non-government organizations, available public data and some personal discussions are used to write this review paper. As the pandemic still on at the time of data been collected and no one knows when it’s going to stop, there can be addition of this paper in the future with updated data. It was a big challenge for Bangladesh to cope-up with the situation as a lower-middle-income economy with one of the world's densest populations. As winter is knocking the door here in Bangladesh, experts are assuming that the second wave will start very soon and the damage can be worst then the first wave. This paper may help the concerns to re-think what was there mistakes and how more organized way they can control the second wave and minimize the damage.

      Volume 5, Issue 3 (2021)

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