Mechanistic Insights on Viral Factors Involved in Asymptomatic COVID-19 Pathogenesis

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.