Conference 2021 Live Talk


Talk title

Molecular interplay between SARS-CoV-2 and human proteins for viral activation and entry, potential drugs and scope for new therapeutics


Authors and Affiliations

Naveen Vankadari1

1. Monash Biomedicine Discovery Institute, Monash University, Clayton 3800 VIC, Australia.




The pandemic Coronavirus Disease 2019 (COVID19) caused by SARS-CoV-2 is a serious public health concern with global mortality of over 1.3 million. Whilst the search for a vaccine is underway, there a several antiviral and antibody treatments being clinically evaluated to fill the “therapeutic gap”. The development of potential drugs or vaccine requires a meticulous understanding of SARS-CoV-2 pathogenicity via key proteins and their interplay with individual host factors to explore the cell entry mechanism.


For understanding the molecular and structural mechanism of SARS-CoV-2 interaction with host protein, the computational approach of virtual molecular docking simulation and molecular dynamics studies were conducted using various tools or programs to unravel real-time dynamics of viral interaction for viral entry. Functional studies performed using the purified proteins and their interaction with the target proteins. A retrospective cohort study of 504 COVID-19 patients from 3 hospitals was done for the antiviral drug (Arbidol, Retanavir and others) treatment studies and to measure the efficacy of selected antiviral medications on mortality via using Odds ratio and lesion absorption based on chest CT scan.


Here we show how the SARS-CoV-2 get activated or primed to infect the host cell via 3 stage processing utilizing host proteins. Our comprehensive structurally studies also show how and why the COVID19 is hypervirulent and the reason for the failure of several antibody treatments and ACE2 blockers. We also structurally demonstrate via molecular dynamics and functional studies how the host proteins CD26, Furin and TMPRSS2 process the viral spike glycoprotein and assist in the viral entry in addition to ACE2. The study also brings forward the potential drugs with structural evidence and its early clinical trials that could block different stages of viral entry.


These molecular, structural, functional studies abet to cognize the detailed mechanism of spike glycoprotein and mode of hijacking the host system for the subsequent viral entry. Understanding the structure and mechanism of SARS-CoV-2 and human protein factual interaction will open the arena of exploring the bona fide therapeutic targets to block different stages of viral entry and new pathways for vaccine development.