Identification of therapeutic target in S2 domain of SARS nCov-2 Spike glycoprotein: Key to design and discover drug candidates for inhibition of viral entry into host cell

Abstract

Humanity is facing a grieve danger of coronavirus disease-19 caused by severe acute respiratory syndrome novel coronavirus-2 (SARS nCov-2) There is an urgent need of therapeutics that can help in overcoming this global pandemic Identifying novel therapeutic target and screening already approved drug is a faster approach in this situation Spike glycoprotein (Sgp) of SARS nCoV-2 is potentials target where in researchers have targeted receptor binding domain (RBD) of S1 domain The S2 domain of Sgp also plays a pivotal role in viral entry, but the mechanism is less understood We analyzed the structure of Sgp S2 domain in pre-fusion state and Heptad repeat region in its post-fusion state available from protein data bank Sgp shows three major regions in S2 domain, the fusion peptide (FP), heptad repeat 1 (HR1) and central helical (CH) region The HR1 region undergoes structural changes by flipping approximately 180∘ and coil up to form a rod like structure during fusion process implying its role in viral entry into the host cell This structural change in S2 domain helices is crucial step, if this process is hindered by targeting the HR1 and CH region then the progression of virus can be stopped Possible binding cavity was identified near the HR1 and CH region in S2 domain and docking-based virtual screening of FDA approved drugs was performed Promising candidates like Troxerutin, Thymopentin and Daclatasvir can be used as therapeutics provided an immediate in-vitro and clinical studies are carried out by research groups Analysis of three-dimensional structure of SARS nCov-2 Spike glycoprotein (Sgp) S2 domain in pre-fusion and post-fusion sate indicate structural changes in S2 domain is vital for viral fusion and entry into host cell Most favorable drug binding site was identified in S2 domain and dock based virtual screening was carried out to obtain hit molecules from a database of already approved FDA drugs [ABSTRACT FROM AUTHOR] Copyright of Journal of Theoretical & Computational Chemistry is the property of World Scientific Publishing Company and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission However, users may print, download, or email articles for individual use This abstract may be abridged No warranty is given about the accuracy of the copy Users should refer to the original published version of the material for the full abstract (Copyright applies to all Abstracts )