ABSTRACT
Coronavirus has brought about three massive outbreaks in the past two decades. Each step of its life cycle invariably depends on the interactions among virus and host molecules. The interaction between virus RNA and host protein (IVRHP) is unique compared to other virus-host molecular interactions and represents not only an attempt by viruses to promote their translation/replication, but also the host's endeavor to combat viral pathogenicity. In other words, there is an urgent need to develop a database for providing such IVRHP data. In this study, a new database was therefore constructed to describe the interactions between coronavirus RNAs and host proteins (CovInter). This database is unique in (a) unambiguously characterizing the interactions between virus RNA and host protein, (b) comprehensively providing experimentally validated biological function for hundreds of host proteins key in viral infection and (c) systematically quantifying the differential expression patterns (before and after infection) of these key proteins. Given the devastating and persistent threat of coronaviruses, CovInter is highly expected to fill the gap in the whole process of the 'molecular arms race' between viruses and their hosts, which will then aid in the discovery of new antiviral therapies. It's now free and publicly accessible at: https://idrblab.org/covinter/.
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is mainly mediated through the interaction between the spike protein (S-pro) of the virus and the host angiotensin-converting enzyme II (ACE2). The attachment of heparan sulfate (HS) to S-pro is necessary for its binding to ACE2. In this study, the binding process of the receptor-binding domain (RBD) of S-pro to ACE2 was explored by enhanced sampling simulations. The free-energy landscape was characterized to elucidate the binding mechanism of S-pro to ACE2 with and without HS fragment DP4. We found that the stability of the T470-F490 loop and the hydrophobic interactions contributed from F486/Y489 in the T470-F490 loop of S-pro are quite crucial for the binding, which is enhanced by the presence of DP4. Our study provides valuable insights for rational drug design to prevent the invasion of SARS-CoV-2.