Molecular and Clinical Investigation of COVID-19: From Pathogenesis and Immune Responses to Novel Diagnosis and Treatment

Abstract

The coronavirus-related severe acute respiratory syndrome (SARS-CoV) in 2002/2003, the Middle East respiratory syndrome (MERS-CoV) in 2012/2013, and especially the current 2019/2021 severe acute respiratory syndrome-2 (SARS-CoV-2) negatively affected the national health systems worldwide. Different SARS-CoV-2 variants, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and recently Omicron (B.1.1.529), have emerged resulting from the high rate of genetic recombination and S1-RBD/S2 mutation/deletion in the spike protein that has an impact on the virus activity. Furthermore, genetic variability in certain genes involved in the immune system might impact the level of SARS-CoV-2 recognition and immune response against the virus among different populations. Understanding the molecular mechanism and function of SARS-CoV-2 variants and their different epidemiological outcomes is a key step for effective COVID-19 treatment strategies, including antiviral drug development and vaccine designs, which can immunize people with genetic variabilities against various strains of SARS-CoV-2. In this review, we center our focus on the recent and up-to-date knowledge on SARS-CoV-2 (Alpha to Omicron) origin and evolution, structure, genetic diversity, route of transmission, pathogenesis, new diagnostic, and treatment strategies, as well as the psychological and economic impact of COVID-19 pandemic on individuals and their lives around the world.

The favorable impacts of silibinin polyphenols as adjunctive therapy in reducing the complications of COVID-19: A review of research evidence and underlying mechanisms

“…In this regard, it is assumed that SARS-CoV-2 bind to angiotensin-converting enzyme 2 (ACE2) receptors of alveolar epithelial cells through the surface glycoproteins [34] . After binding, the spike proteins of SARS-COV-2 are fragmented via acid-dependent proteolysis through TMPRRS2, cathepsin, or furin protease, and viruses enter the cytoplasm via endocytosis [35] , [36] . Then, the genomes of the viruses release and translated into target proteins in the cytoplasm.…”

COVID-19 Pathogenesis and Diagnosis

“…At similar dates, the International Committee on Taxonomy of Viruses named this new coronavirus as SARS-coronavirus-2 (CoV-2). The first case of COVID-19 in our country was detected on March 11, when the WHO declared the disease as a pandemic (1,2,3,4,5). In this article, the basic virology pathogenesis and new approaches and diagnostic methods of SARS-CoV-2, which causes COVID-19, are reviewed.…”

“…Next, the viral particles bud into the endoplasmic reticulum-Golgi intermediate compartment. Finally, the vesicles containing the virus particles then fuse with the plasma membrane to release the virus (4,5,7).…”

Current strategies for SARS-CoV-2 molecular detection

“…109,110 Many variants have appeared, especially in the spikes of SARS-CoV-2 RBD and receptor-binding motif (RBM), through a broad spectrum of point mutations, recombination, deletions, and amino acid substitutions, such as alpha (a), beta (b), gamma (g), delta (d), and recently the Omicron variant. 111 The Omicron variant (B.1.1.529) was rst identied in Botswana and South Africa in November 2021, and several sub-lineages (e.g., BA.1, BA.1.1, BA.2, BA.3, BA.4, BA.5, and BA.2.12.1) were developed, by far replacing other VOCs during the following weeks among many countries and regions in the world. 112 The lineage poses great challenges to current detection, vaccines, and treatment, largely due to the most striking characteristic of the variant, its outrageous number of mutations.…”