SARS-CoV-2: A Virological, Pathological, and Evolutionary Guide

Author(s): Muhammad Waqas Nasir, Wangjing, Xiangyu Zhang, Mahir Azmal, Ajit Ghosh, Yong Gao

The COVID-19 pandemic, driven by SARS-CoV-2, has profoundly affected global public health and catalyzed an unprecedented surge in scientific discovery. This comprehensive review examines SARS-CoV-2 from evolutionary, virological, and pathological perspectives, providing an in-depth analysis of the structural and functional roles of key viral proteins, including spike (S), envelope (E), nucleocapsid (N), and membrane (M) in viral replication, immune system evasion, and host cell interactions. Mechanisms of viral entry are explored, highlighting the interplay between the viral spike protein and host cellular receptors such as ACE2, TMPRSS2, CD147, and Neuropilin-1, as well as their associated entry pathways. The review further discusses the genomic architecture of SARS-CoV-2, its tropism for specific tissues, and its remarkable capacity for adaptation and pathogenicity. The emergence and global dissemination of SARS-CoV-2 variants including both variants of concern and variants of interest are analyzed with respect to genetic mutations, transmission dynamics, and public health implications. Diagnostic advancements are addressed, with particular focus on gold-standard RT-PCR testing, CRISPR-based detection methods, and their roles in effective disease surveillance. Therapeutic strategies targeting both viral and host factors are evaluated, alongside immunological phenomena such as immune evasion, cytokine storm syndromes, and the regulatory influence of non-coding RNAs. In conclusion, this review reflects on the future trajectory of SARS-CoV-2, highlighting ongoing immune challenges, the likely transition to endemicity, and the necessity for sustained global preparedness.