Whole genome analysis and homology modeling of SARS-CoV-2 Indian isolate reveals potent FDA approved drug choice for treating COVID-19.

Coronaviruses have caused enough devastation in the last two decades. These viruses have some rare features while sharing some common features. Novel coronavirus disease (nCoV-19) caused an outbreak with a fatality rate of 5%. It emerged from China and spread into many countries. The present research focused on genome analysis of Indian nCoV-19 Isolate and its translational product subjected to homology modeling and its subsequent molecular simulations to find out potent FDA approved drug for treating COVID-19. Phylogenetic analysis of SARS-CoV-2 Indian isolate shows close resemblance with 17 countries SARS-CoV-2 isolates. Homology modeling of four non-structural proteins translational product of Indian SARS-CoV-2 genome shows high similarity and allowed regions with the existing PDB deposited SARS-CoV-2 target proteins. Finally, these four generated proteins show more affinity with cobicistat, remdesivir and indinavir out of 14 screened FDA approved drugs in molecular docking which is further proven by molecular dynamics simulation and MMGBSA analysis of target ligand complex with best simulation trajectories. Overall our present research findings is that three proposed drugs namely cobicistat, remdesivir and indinavir showed higher interaction with the model SARS-CoV-2 viral target proteins from the Indian nCoV-19 isolate. These compounds could be used as a starting point for the creation of active antiviral drugs to combat the deadly COVID-19 virus during global pandemic and its subsequent viral infection waves across the globe.Communicated by Ramaswamy H. Sarma.

Molecular insights of hyaluronic acid-hydroxychloroquine conjugate as a promising drug in targeting SARS-CoV-2 viral proteins.

In-silico anti-viral activity of Hydroxychloroquine (HCQ) and its Hyaluronic Acid-derivative (HA-HCQ) towards different SARS-CoV-2 protein molecular targets were studied. Four different SARS-CoV-2 proteins molecular target i.e., three different main proteases and one helicase were chosen for In-silico anti-viral analysis. The HA-HCQ conjugates exhibited superior binding affinity and interactions with all the screened SAR-CoV-2 molecular target proteins with the exception of a few targets. The study also revealed that the HA-HCQ conjugate has multiple advantages of efficient drug delivery to its CD44 variant isoform receptors of the lower respiratory tract, highest interactive binding affinity with SARS-CoV-2 protein target. Moreover, the HA-HCQ drug conjugate possesses added advantages of good biodegradability, biocompatibility, non-toxicity and non-immunogenicity. The prominent binding ability of HA-HCQ conjugate towards Mpro (PDB ID 5R82) and Helicase (PDB ID 6ZSL) target protein as compared with HCQ alone was proven through MD simulation analysis. In conclusion, our study suggested that further in-vitro and in-vivo examination of HA-HCQ drug conjugate will be useful to establish a promising early stage antiviral drug for the novel treatment of COVID-19.