SARS‐CoV‐2‐specific virulence factors in COVID‐19

Abstract

The paucity of knowledge about severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐specific virulence factors has greatly hampered the therapeutic management of patients with coronavirus disease 2019 (COVID‐19). Recently, a cluster of studies appeared, which presented empirical evidence for SARS‐CoV‐2‐specific virulence factors that can explain key elements of COVID‐19 pathology. These studies unravel multiple structural and nonstructural specifics of SARS‐CoV‐2, such as a unique FURIN cleavage site, papain‐like protease (SCoV2‐PLpro), ORF3b and nonstructural proteins, and dynamic conformational changes in the structure of spike protein during host cell fusion, which give it an edge in infectivity and virulence over previous coronaviruses causing pandemics. Investigators provided robust evidence that SARS‐CoV‐2‐specific virulence factors may have an impact on viral infectivity and transmissibility and disease severity as well as the development of immunity against the infection, including response to the vaccines. In this article, we are presenting a summarized account of the newly reported studies.

Angiotensin System Polymorphisms’ in SARS-CoV-2 Positive Patients: Assessment Between Symptomatic and Asymptomatic Patients: A Pilot Study

“… 1–3 The clinical spectrum of SARS-CoV-2 infection varies from the most frequent asymptomatic or mild symptomatic forms to severe progressive pneumonia and death, with specific virulence factors to achieve mortality rates around 3%. 4 …”

Drosophila, a powerful model to study virus-host interactions and pathogenicity in the fight against SARS-CoV-2

“…These differences might be explained by the different purification methods and cell lines used in each study, thus additional studies are warranted. Several recent reports have investigated these virus-host interactions in more detail, using in vitro models to identify virus-mediated disrupted pathways and cellular damage [ 5 ]. Their findings have highlighted differences between the coronaviruses, singled out the most toxic virus proteins, provided additional insights into host protein targets and underlying pathogenic mechanisms, and identified and tested compounds for therapeutic intervention.…”

Expression of SARS-CoV-2 Host Cell Entry Factors in Immune System Components of Healthy Individuals and Its Relevance for COVID-19 Immunopathology

“…With current level of evidence, host cell expressions of ACE2 and the tissue proteases (TMPRSS2/CTSL and FUR-IN) are considered essential conditions for SARS-CoV-2 infection (6,7,11), and a high expression of ACE2 alone does not ensure that a cell will be infected (25).…”

“…T he ongoing pandemic of coronavirus disease-2019 (COVID-19) caused by the novel strain of coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has affected millions of lives globally. SARS-CoV-2, an enveloped positive sense single-stranded RNA virus belongs to genus betacoronavirus of the Coronaviridae family that includes SARS-CoV-1 and MERS-CoV: the causative agents of respiratory syndrome outbreaks in recent past (11,14).…”

“…The receptor recognition and the ensuing fusion are critical for viral infections that is facilitated by the entry associated protein transmembrane serine protease 2 (TMPRSS2) or Cathepsin L (CTSL) in concert with FURIN, a host cell associated protease that mediates the cleavage of the viral spike (S) protein (6,7). FURIN has shown to be unique to SARS-CoV-2 and essential for successful viral invasion of the host cells (11).…”