Preprint Review Version 2 Preserved in Portico This version is not peer-reviewed

COVID-19 Pandemic: Insights into Structure, Function, and hACE2 Receptor Recognition by SARS-CoV-2

Version 1 : Received: 14 May 2020 / Approved: 15 May 2020 / Online: 15 May 2020 (18:04:23 CEST)
Version 2 : Received: 9 July 2020 / Approved: 10 July 2020 / Online: 10 July 2020 (16:21:17 CEST)

A peer-reviewed article of this Preprint also exists.

Journal reference: Plos Pathogens 2020, 16
DOI: 10.1371/journal.ppat.1008762

Abstract

SARS-CoV-2 is a newly emerging, highly transmissible, and pathogenic coronavirus in humans, which has caused global public health emergency and economic crisis. To date, millions of infections and thousands of deaths have been reported worldwide, and the numbers continue to rise. Currently, there is no specific drug or vaccine against this deadly virus; therefore, there is a pressing need to understand the mechanism through which this virus enters the host cell. Viral entry into the host cell is a multistep process in which SARS-CoV-2 utilizes the receptor binding domain of the spike glycoprotein (S) to recognize ACE2 receptors on the human cells; this initiates host cell entry by promoting viral-host cell membrane fusion through large scale conformational changes in the S protein. Receptor recognition and fusion are critical and essential steps of viral infections and are key determinants of the viral host range and cross-species transmission. In this review, we summarize the current knowledge on the origin and evolution of SARS-CoV-2 and the roles of key viral factors. We discuss the RNA dependent RNA polymerase structure of SARS-CoV-2, its significance in drug discovery, and explain the receptor recognition mechanisms of coronaviruses. We provide a comparative analysis of the SARS-CoV and SARS-CoV-2 S proteins, receptor-binding specificity, and discuss the differences in their antigenicity based on biophysical and structural characteristics.

Subject Areas

COVID-19; SARS-CoV; SARS-like coronavirus; 2019-nCoV; SARS-CoV-2; angiotensin-converting enzyme 2 (ACE2); RdRp; Remdesivir; and neutralizing antibody

Comments (1)

Comment 1
Received: 10 July 2020
Commenter: Vikash Verma
Commenter's Conflict of Interests: Author
Comment: The original version of this manuscript was favorably reviewed by three experts in the field. Following the advice of reviewers, we have substantially restructured the manuscript and added a new section (4.1), where we discuss the structure of RNA dependent RNA polymerase of SARS-CoV-2, and its significance in drug discovery. Further, we have removed digressive sections describing “therapeutic interventions to COVID-19”, and “environmental effects on SARS-CoV-2 stability” as advised by the reviewers.
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