SARS-CoV-2 and Emerging Variants: Unmasking Structure, Function, Infection, and Immune Escape Mechanisms

Abstract

As of April 1, 2022, over 468 million COVID-19 cases and over 6 million deaths have been confirmed globally. Unlike the common coronavirus, SARS-CoV-2 has highly contagious and attracted a high level of concern worldwide. Through the analysis of SARS-CoV-2 structural, non-structural, and accessory proteins, we can gain a deeper understanding of structure-function relationships, viral infection mechanisms, and viable strategies for antiviral therapy. Angiotensin-converting enzyme 2 (ACE2) is the first widely acknowledged SARS-CoV-2 receptor, but researches have shown that there are additional co-receptors that can facilitate the entry of SARS-CoV-2 to infect humans. We have performed an in-depth review of published papers, searching for co-receptors or other auxiliary membrane proteins that enhance viral infection, and analyzing pertinent pathogenic mechanisms. The genome, and especially the spike gene, undergoes mutations at an abnormally high frequency during virus replication and/or when it is transmitted from one individual to another. We summarized the main mutant strains currently circulating global, and elaborated the structural feature for increased infectivity and immune evasion of variants. Meanwhile, the principal purpose of the review is to update information on the COVID-19 outbreak. Many countries have novel findings on the early stage of the epidemic, and accruing evidence has rewritten the timeline of the outbreak, triggering new thinking about the origin and spread of COVID-19. It is anticipated that this can provide further insights for future research and global epidemic prevention and control.

Enhanced stability of the SARS CoV-2 spike glycoprotein trimer following modification of an alanine cavity in the protein core

“…Conserved neutralization epitopes external to the RBD and NTD have also been identified including within the stem helix of S2 (12, 23, 24). Immunity induced by natural infection or vaccination is believed to be driving the emergence of variants of concern (VOCs) which primarily contain mutations in the RBD and NTD (25–28). Variants of concern are associated with successive waves of infections across the globe with Alpha, Delta and now Omicron infections, respectively, dominating the pandemic.…”

“…Conserved neutralization epitopes external to the RBD and NTD have also been identified including within the stem helix of S2 (12,23,24). Immunity induced by natural infection or vaccination is believed to be driving the emergence of variants of concern (VOCs) which primarily contain mutations in the RBD and NTD (25)(26)(27)(28).…”

The Impact of COVID-19 Pandemic on Dermatological Conditions: A Novel, Comprehensive Review

“…Since its first appearance in 2019, variants of SARS-CoV-2 have continued to emerge. Among the most common variants, the Omicron variant is responsible for the largest surge of COVID cases since 2019 [ 4 ]. However, the Omicron variant has caused significantly less morbidity and mortality.…”

“…However, the Omicron variant has caused significantly less morbidity and mortality. Variants of SARS-CoV-2 preferentially infect the airway mucosa [ 4 ]. As such, respiratory symptoms such as fever, cough, and shortness of breath are among the most common manifestations of the infection [ 1 , 4 , 5 ].…”

“…Variants of SARS-CoV-2 preferentially infect the airway mucosa [ 4 ]. As such, respiratory symptoms such as fever, cough, and shortness of breath are among the most common manifestations of the infection [ 1 , 4 , 5 ]. However, many factors affect the prognosis and severity of the disease [ 4 , 5 ].…”