Abstract
SARS-CoV-2 infection may cause asymptomatic, pre-symptomatic or symptomatic COVID-19
disease. While symptomatic infections are at the centre stage for disease diagnosis and treatment, asymptomatic
and pre-symptomatic cases heighten the challenge of transmission tracking ultimately leading to
failure of control interventions. Asymptomatic cases appear due to a variety of host and viral factors and
contribute substantially to the total number of infections. Through this article, we have tried to assemble
existing information about the role of viral factors and mechanisms involved in the development of
asymptomatic COVID-19. The significance of ‘PLpro’- a protease of Nidovirales order that removes
ubiquitin and ISG15 from host proteins to regulate immune responses against the virus and hence disease
presentation has been highlighted. PL-pro dampens inflammatory and antiviral responses, leading to
asymptomatic infection. 11083G>T-(L37F) mutation in ‘Nsp6’ of SARS-CoV-2 also diminishes the innate
immune response leading to asymptomatic infections. It is, therefore, pertinent to understand the role
of proteins like PLpro and Nsp6 in SARS-CoV-2 biology for the development of transmission control
measures against COVID-19. This review focuses on viral molecular mechanisms that alter disease severity
and highlights compounds that work against such regulatory SARS-CoV-2 proteins.
Keywords:
Asymptomatic COVID-19, SARS-CoV-2, PLpro, deubiquitination, deISGylation, DUB domain.
Graphical Abstract
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