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Virology: Current Research

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, Mihael H. Polymeropoulo

    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 viamultiple 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 SARS-CoV-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. 

    Commentary 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 4, Issue 2 (2020)

      Research Article Pages: 1 - 6

      Anti-Retroviral Therapy and Serum Protein Levels in HIV-1 Seropositive Patients: A Five-Year Retrospective Study

      Akor Egbunu Shedrack, Musa Haruna, Eneojo-Abah Eleojo Gloria, Yisa Benjamin Nma, Emmanuel Friday Titus, Dickson Achimugu Musa, Joel Ikojo Oguche, Serah Shaibu, Salami Tijani, David Bukbuk and Samuel Eneojo Abah*

      Background: Serum proteins designated as liver function biomarkers are used to evaluate patients for hepatic dysfunction. Hepatic effect of Anti-Retroviral Therapy (ART) needs further studies in HIV mono-infected patients. In this study, clinically defined patient datasets were analysed for protein levels in HIV-1 mono-infected seropositive patients with and without ART.

      Materials and methods: Data were collected for the study groups, consisting of the control group and HIV-1 mono-infected seropositive patients with and without ART and were analysed statistically for differences among the groups. All subjects in the patient groups attended University of Maiduguri Teaching Hospital, Nigeria for a period of 5 years.

      Result: The protein levels on initiation of ART were significantly higher than baseline levels (prior to ART). However, continuous use of ART for 5-year period did not induce any further significant change in protein levels. Receiver Operating Characteristic (ROC) curves shows that both Albumin (ALB) and Total protein (TP) levels discriminated among the study groups. The baseline levels of ALB in seropositive patients are significantly lower to levels on initiation of ART.

      Conclusion: Continuous ART did not cause any further significant change in levels of liver function proteins than was observed on ART initiation. Hence, liver damage on continuous ART is not implied. Both ALB and TP levels could be important in HIV management of patients. Initiation of ART appears to elevate the low ALB level via a yet unknown mechanism and indicates possible role of ALB in ART mechanism of action.

      Research Article Pages: 1 - 9

      Implications of Haplotype Switching for the Origin and Global Spread of COVID-19

      Edward J. Steele*, Reginald M. Gorczynski, Herbert Rebhan, Patrick Carnegie, Robert Temple, Gensuke Tokoro, Alexander Kondakov, Stephen G. Coulson, Dayal T. Wickramasinghe and N. Chandra Wickramasinghe*

      When analysed in patients at epicentres of outbreaks over the first three months of the 2020 pandemic, the virus responsible for COVID-19 cannot be classed as a rapidly mutating virus. It employs a haplotype-switching strategy most likely driven by APOBEC and ADAR cytosine and adenosine deamination events (C>U, A>I) at key selected sites in the ~ 30,000 nt positive sense single-stranded RNA genome (Steele and Lindley 2020). Quite early on (China, through Jan 2020) the main haplotype was L with a minor proportion of the S haplotype. By the time of the explosive outbreaks in New York City (mid-to late-March 2020) the haplotype variants expanded to at least 13. The COVID-19 genomes analysed at the main sites of exponential increases in cases and deaths over a 2 week time period (explosive epicentres) such as Wuhan and New York City showed limited mutation per se of the main haplotypes engaged in disease. When mutation was detected it was usually conservative in terms of significant alterations to protein structure. The coronavirus haplotypes whether in Wuhan, West Coast USA, Spain or New York differ by no more than 2-9 coordinated nucleotide changes and all genomes are thus ≥ 99.98% identical to each other. Further, we show that the most similar SARS-like CoV animal virus sequences (bats, pangolins) could not have caused the assumed zoonotic event setting off this explosive pandemic in Wuhan and regions: zoonotic causation via a Chinese wild bat SL-CoV reservoir jumping to humans by an intermediate amplifier (e.g. pangolins) is clearly not possible on the basis of the available data. We also discuss the evidence for airborne transmission of COVID-19 as the main infection route and highlight outbreaks on certain ships at sea consistent with their hypothesised cosmic origins. We conclude that the virus originated as a pure genetic strain in a life-bearing carbonaceous meteorite which was first deposited in the tropospheric jet stream over Wuhan. Over the next month or so this viral-laden dust cloud not only descended through the troposphere to target Wuhan and its environs, but was also transported in a Westerly direction through the mid-latitude northern jet stream causing explosive in-fall events sequentially over Iran, Italy, Spain and then New York City in the early months of the pandemic to the end of March 2020.

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