COVID-19 pandemic: Insights into structure, function, and hACE2 receptor recognition by SARS-CoV-2

Abstract

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a newly emerging, highly transmissible, and pathogenic coronavirus in humans that has caused global public health emergencies and economic crises. 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(s) 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 (RBD) of the spike (S) glycoprotein to recognize angiotensin-converting enzyme 2 (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 structure of RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 and its significance in drug discovery and explain the receptor recognition mechanisms of coronaviruses. Further, we provide a comparative analysis of the SARS-CoV and SARS-CoV-2 S proteins and their receptor-binding specificity and discuss the differences in their antigenicity based on biophysical and structural characteristics.

Immunogenicity and crossreactivity of antibodies to the nucleocapsid protein of SARS-CoV-2: utility and limitations in seroprevalence and immunity studies

“…In addition, it is essential to understand immunity to COVID-19 disease. Previous knowledge on other related coronaviruses and the prompt sequencing of the SARS-CoV-2 genome early in the pandemic allowed to identify the spike (S) 1 and the nucleocapsid (N) 2 structural proteins as major targets of antibodies. Consequently, both antigens constituted the basis for most immunoassays developed to study COVID-19 distribution and protective immune responses.…”

Comparative in vitro analysis of inhibition of rhinovirus and influenza virus replication by mucoactive secretolytic agents and plant extracts

“…Annual influenza epidemics are estimated to result in about 3 to 5 million cases of severe illness, and about 290,000 to 650, 000 respiratory deaths [6]. Measures of prevention and treatment of rhinovirus and coronavirus infections do not exist, albeit several virus proteins e. g. viral capsid, protease, and polymerase proteins have been identified as valid targets of inhibitors [7][8][9]. Even though influenza vaccines do exist, they are suboptimal applied [10][11][12][13].…”

Targeting transcriptional regulation of SARS-CoV-2 entry factorsACE2andTMPRSS2

“…The genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the coronavirus responsible for COVID-19, is a positive, single-stranded RNA that encodes nonstructural and structural proteins required for the viral life cycle. Among these are its four main structural proteins: N, Nucleocapsid; E, Envelope; M, Membrane; and S, Spike ( 2 ). The Spike glycoprotein plays a pivotal role in SARS-CoV-2 infection by recognizing and attaching to the angiotensin-converting enzyme 2 (ACE2) transmembrane protein on host cells ( 3 ).…”