Elucidating the Interactions Between Heparin/Heparan Sulfate and SARS-CoV-2-Related Proteins-An Important Strategy for Developing Novel Therapeutics for the COVID-19 Pandemic.

Mingjia Yu,Tianji Zhang,Hongmei Li,Jin-Ping Li,Wei Zhang,Qianyun Sun

doi:10.3389/fmolb.2020.628551

Abstract

Owing to the high mortality and the spread rate, the infectious disease caused by SARS-CoV-2 has become a major threat to public health and social economy, leading to over 70 million infections and 1. 6 million deaths to date. Since there are currently no effective therapeutic or widely available vaccines, it is of urgent need to look for new strategies for the treatment of SARS-CoV-2 infection diseases. Binding of a viral protein onto cell surface heparan sulfate (HS) is generally the first step in a cascade of interaction that is required for viral entry and the initiation of infection. Meanwhile, interactions of selectins and cytokines (e.g., IL-6 and TNF-α) with HS expressed on endothelial cells are crucial in controlling the recruitment of immune cells during inflammation. Thus, structurally defined heparin/HS and their mimetics might serve as potential drugs by competing with cell surface HS for the prevention of viral adhesion and modulation of inflammatory reaction. In this review, we will elaborate coronavirus invasion mechanisms and summarize the latest advances in HS–protein interactions, especially proteins relevant to the process of coronavirus infection and subsequent inflammation. Experimental and computational techniques involved will be emphasized.

Highlights

The whole world is facing the deadly coronavirus disease 2019 (COVID-19) outbreak caused by the coronavirus (CoV) SARS-CoV-2, which has been far beyond the outbreaks caused by the other two major coronaviruses (SARS and MERS) in the past 20 years (Drosten et al, 2003; Zaki et al, 2012)
Studies suggested that different compositions in heparan sulfate (HS) could impact the tropism of viruses (Wickramasinghe et al, 2011) and HS co-receptors on host cell surface leads to conformational changes of the CoVs’ S proteins (Lang et al, 2011; Milewska et al, 2014; Mycroft-West et al, 2020a), possibly through the formation of a ternary complex (Clausen et al, 2020) (Figure 3). These findings suggested that the HS–S protein interactions might serve as a potential target to attenuate virus infection
This study demonstrated that the SARS-CoV-2 S protein may mediate an enhanced interaction with HS analogs and heparinoid derivatives compared to severe acute respiratory syndrome coronavirus (SARSCoV)-1 by the evolution of Lys444 and Glu354 (SARS-CoV-1) to Thr444 and Asn354 (SARS-CoV-2), respectively

Summary

Introduction

The whole world is facing the deadly coronavirus disease 2019 (COVID-19) outbreak caused by the coronavirus (CoV) SARS-CoV-2, which has been far beyond the outbreaks caused by the other two major coronaviruses (SARS and MERS) in the past 20 years (Drosten et al, 2003; Zaki et al, 2012). It has been known that CoVs often initially interact with cell surface molecules to promote their binding to specific receptors.

Results

Conclusion