An in-silico investigation of potential natural polyphenols for the targeting of COVID main protease inhibitor.

The deadliest recent pandemic outbreak of COVID-19 disease has severely damaged the socio-economic health of the people globally. Due to unavailability of any effective vaccine or treatment the human beings are still struggling to overcome the pandemic condition. In an attempt to discover anti-COVID molecule, we used in-silico approach and reported 160 natural polyphenols to identify the most promising druggable HITs that can further used for drug discovery process. The co-crystallized structure COVID protease enzyme (PDB id 6LU7) was used. HTVS, MD simulation, binding energy calculations and in-silico ADME calculation were done and analyzed. Depending upon the scores three compounds galangin, nalsudaldain and rhamnezine were identified and the docking score were found to be -7.704, -6.51, -4.212 respectively. These docked complexes were further subjected to MD simulation runs over a 100 ns time and the RMSD and RMSF values were determined. The RMSD values of three compounds were found to be 2.9 Å, 7.6 Å & 9.5 Å respectively and the lowest RMSF values suggested the steady stability of ligand-protein complexes. The binding free energies (ΔG) of compounds with protein were found to be -49.8, -56.45, -62.87 kJ/mole. Moreover, in-silico ADME calculations indicated the drug likeliness properties of these molecules. By considering all these in-silico results the identified HITs would be the most probable anti-COVID drug molecules that can be further taken in wet lab and can act as lead for development of newer inhibitor of COVID-19 main protease enzyme.

Design & discovery of small molecule COVID-19 inhibitor via dual approach based virtual screening and molecular simulation studies.

The emerged COVID-19 (SARS corona virus) pandemic leads to severe or fatal respiratory tract infections affecting millions of people worldwide since its outbreak. The situation needs the newer molecule to control the infections as the pandemic had very badly affected the health and socioeconomic conditions of human being. CoV-2 main protease is considered to be key enzyme by targeting which we can design or develop the drug candidate. The active fitting and binding of any molecule depends upon the shape and electrostatic properties of ligand complementary to the receptor site. In this study ZINC13 database, a drug like subset (13,195,609 molecules) was subjected to shape and electrostic based virtual screening (VROCS & EON software) and followed by molecular modelling studies using docking and molecular dynamics simulation. Further the drug ability of identified candidate was predicted by the SiteMap analysis. The best shape and electrostatic similarities were observed between ZINC19973962 and reference molecule. The Tamintoshape and Tanimotoelectrostatic was found to be 0.667 and 0.022 respectively. The molecule also displayed the identical binding pattern with docking score -7.964 and this interaction was further validated by the molecular dynamics simulations. The RMSD & RMSF values were found to be 1.5 Å and1.8 Å respectively suggesting the stability of complex and very low fluctuation in ligand-protein complex over the entire MD simulation run. SiteMap analysis showed the identical Dscore of reference and identified HIT that indicated the molecule ZINC19973962 would be the promising druggable candidate against COVID main protease enzyme and can be used as lead molecule for the development of anti-COVID molecule.

Kefir: A protective dietary supplementation against viral infection.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a recently discovered coronavirus termed 'severe acute respiratory syndrome coronavirus 2' (SARS-CoV-2). Several scholars have tested antiviral drugs and compounds to overcome COVID-19. 'Kefir' is a fermented milk drink similar to a thin yogurt that is made from kefir grains. Kefir and its probiotic contents can modulate the immune system to suppress infections from viruses (e.g., Zika, hepatitis C, influenza, rotaviruses). The antiviral mechanisms of kefir involve enhancement of macrophage production, increasing phagocytosis, boosting production of cluster of differentiation-positive (CD4+), CD8+, immunoglobulin (Ig)G+ and IgA+ B cells, T cells, neutrophils, as well as cytokines (e.g., interleukin (IL)-2, IL-12, interferon gamma-γ). Kefir can act as an anti-inflammatory agent by reducing expression of IL-6, IL-1, TNF-α, and interferon-γ. Hence, kefir might be a significant inhibitor of the 'cytokine storm' that contributes to COVID-19. Here, we review several studies with a particular emphasis on the effect of kefir consumption and their microbial composition against viral infection, as well as discussing the further development of kefir as a protective supplementary dietary against SARS-CoV-2 infection via modulating the immune response.