Andrographolide binds to spike glycoprotein and RNA-dependent RNA polymerase (NSP12) of SARS-CoV-2 by in silico approach: a probable molecule in the development of anti-coronaviral drug

Lokanathan Srikanth,Potukuchi Venkata Gurunadha Krishna Sarma

doi:10.1186/s43141-021-00201-7

Lokanathan Srikanth, Potukuchi Venkata Gurunadha Krishna Sarma

Open Access

https://doi.org/10.1186/s43141-021-00201-7

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Abstract

The SARS-CoV-2 belongs to Coronaviridae family infects host cells by the interaction of its spike glycoprotein and angiotensin-converting enzyme 2 (ACE 2) of host cells. Upon entry, the virus uses its RNA dependent RNA polymerase (NSP12) for transcribing its genome to survive in the cell and spread its infection. The protein sequences of receptor-binding domain (RBD) of spike glycoprotein, and NSP12 exhibits high homology in the family of Coronoviridae and are ideal candidates for the development of anti-coronaviral drugs. In the quest to identify inhibitory molecules against these proteins, we searched several molecules that are present in naturally occurring medicinal plants database. Andrographolide which is largely present in the leaf extracts of Andrographis paniculata (AP) and is known to exhibit antiviral, antibacterial, and stabilizes Th1/Th2/Th17 responses; taking this clue, we used in silico approaches to see the binding of andrographolide to RBD and NSP12 molecules. Our docking results showed very strong affinity of andrographolide to RBD and NSP12 of the SARS-CoV-2 virus with dock scores of −10.3460 for RBD and −10.7313 for NSP12 indicating andrographolide acts as an inhibitor of RBD and NSP12. These unique properties of andrographolide, AP extract, can be tested as anti-coronaviral drug.

Highlights

The pandemic caused by SARS-CoV-2 which has emerged from China has devastated whole humanity
Among the NSP12, i.e., RNA-dependent RNA polymerase(RdRP) of SARS-CoV-2 reported at various countries like Australia (QJR96151.1), Belgium (QIB84671.1), France (QJT73032.1), Guangzhou (China) (QJQ84086.1), India (QJQ28427.1), Japan (BCF74567.1), and the USA (QJP03561.1) were analyzed with multiple sequence alignment (MSA) followed by super imposing their structures being built by using Modeller 9.24 taking the three-dimensional structure of PDB ID: 6M71 as template
Analysis of spike glycoprotein of SARS Cov-2 The findings of MSA for spike glycoprotein with other members of coronavirus (SARS, MERS, HKU4, and HKU1) indicate conserved S1 and S2 domains which are the feature in spike protein of Coronaviridae family; the receptor-binding domain (RBD) region of coronavirus is highly variable which makes it defensive to bind and enter the host cells (Fig. 1A, B)

Summary

Introduction

The pandemic caused by SARS-CoV-2 which has emerged from China has devastated whole humanity. Specific RBDreceptor binding determines if a cell can be infected and serves as a target for therapeutic developments to treat diseases caused by coronaviruses [7, 8] This SARS-CoV-2 infection to the host cells, coronaviruses utilizes a multi-subunit RNA-synthesis complex of viral non-structural proteins (NSP) responsible for the replication and transcription of the viral genome. The Nterminal of NSP12 contains a common structure which is conserved in all coronaviral polymerases as a large structure having kinase-like fold bound by two NSP8 molecules This demonstrates NSP12 complex a potent therapeutic target in the development anti-coronaviral drugs [9]. One of the approved lists of drugs in the treatment of COVID-19 is remdesivir; it inhibits NSP 12 and thereby prevents RNA synthesis and kills the virus This remdesivir molecular formula is C27H35N6O8P; the structure appears to have prominent naphthalene ring [9]. We used in silico approach to dock andrographolide structure to RBD and NSP12 protein structures of SARS-CoV-2 to predict that AP extract can be used for anti-coronaviral treatment

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