The novel coronavirus (nCOV-2019) outbreak has put the world on
edge, causing millions of cases and hundreds of thousands of
deaths all around the world, as of June 2020, let alone the
societal and economic impacts of the crisis. The spike protein
of nCOV-2019 resides on the virion’s surface mediating
coronavirus entry into host cells by binding its receptor
binding domain (RBD) to the host cell surface receptor protein,
angiotensin converter enzyme (ACE2). Our goal is to provide a
detailed structural mechanism of how nCOV-2019 recognizes and
establishes contacts with ACE2 and its difference with an
earlier severe acute respiratory syndrome coronavirus (SARS-COV)
in 2002 via extensive molecular dynamics (MD) simulations.
Numerous mutations have been identified in the RBD of nCOV-2019
strains isolated from humans in different parts of the world. In
this study, we investigated the effect of these mutations as
well as other Ala-scanning mutations on the stability of the
RBD/ACE2 complex. It is found that most of the naturally
occurring mutations to the RBD either slightly strengthen or
have the same binding affinity to ACE2 as the wild-type
nCOV-2019. This means that the virus had sufficient binding
affinity to its receptor at the beginning of the crisis. This
also has implications for any vaccine design endeavors since
these mutations could act as antibody escape mutants.
Furthermore, in silico Ala-scanning and long-timescale MD
simulations highlight the crucial role of the residues at the
interface of RBD and ACE2 that may be used as potential
pharmacophores for any drug development endeavors. From an
evolutional perspective, this study also identifies how the
virus has evolved from its predecessor SARS-COV and how it could
further evolve to become even more infectious.