SARS CoV-2;a closer look at the agent of the pandemic of modern times

ABSTRACT

Due to the COVID-19 pandemic, as of September 2021, a total of 222,309,456 people were infected in the world and a total of 4,592,685 patients were lost. The pandemic, which has a fatality rate of around 2%, has made and continues to make us live thhrough all experiences of epidemics that we have only read about in Annals of Medicine and Microbiology and that deeply affected the World at their times. The virus causing the pandemic has a positive polarity RNA genome of 30,000 bases and produces a total of 29 proteins. Of these proteins, 4 are structural, 16 are nonstructural, and 9 are accessory proteins. SARS-CoV-2 is an enveloped RNA virus with a diameter of 150-200 nm, has an S (spike-spike-tassel) glycoprotein on its surface, which, like other coronaviruses, creates the crown appearance unique to these viruses. After the S protein is synthesized as a polyprotein, it is cleaved into S1 and S2 subunits. The S1 subunit binds to the target cell, and the S2 subunit performs fusion with the cell membrane to be infected. Since these functions are critical features of a successful viral infection, the S protein is the main target of all interventions to prevent virus infection. In this context, the main target of neutralizing antibodies and drugs to stop virus infection before it starts is the S protein. The S protein has a trimer structure similar to hemagglutinin in influenza virus and contains the fusion peptide that becomes exposed during transition from the prefusion configuration to the fusion configuration and facilitates the fusion function with the cellular/endosomal membranes. Apart from the S protein, SARS-CoV-2 has structural proteins known as E (envelope), M (membrane), and N (nucleocapsid) proteins;The N protein binds to the RNA genome and together with the S, E and M proteins and the RNA genome form the virion. While SARS-CoV-2 S protein attaches to cells using Cellular Angiotensin Converting Enzyme 2 (HCoV- NL63, SARS-CoV and SARS-CoV-2), other coronaviruses use different receptors (Aminopeptidase N-HCoV-229E;dipeptidyl peptidase 4- MERS-CoV). Unlike viruses in this group, the SARS CoV-2 S1 protein with receptor binding domain (RBD) has a cleavage site made up of polybasic amino acids at the S1-S2 border and used by the cellular furin protease, which is believed to provide advantages to the virus in proteolytic cleavage, cell tropism, virulence and pathogenicity. ACE-2 is important in the renin-angiotensin-aldosterone system and although it is rarely found in the circulation, it is widely expressed in organs and is an enzyme involved in the regulation of blood pressure and fluid balance. Following intracellular entry and fusion of membranes, the SARS-CoV-2 genome is released into the cytoplasm and gene expression proceeds as a temporally and spatially well-regulated process. Non-structural proteins, which are produced from direct translation of ORF1a and ORF1b regions of positive sense genomic RNA, form the replication and transcription complex. These complexes establish the infrastructure for the next steps. The common features of coronaviruses such as cytoplasmic replication, viral gene expression through sub-genomic nested set messages, exocytosis of mature virions within vesicles occur in SARS-CoV-2 as well. One of the most important problems in the COVID-19 pandemic has been the emergence of variant viruses. These viruses adversely affecting the transmission rate, virulence, clinical course, and the effectiveness of the diagnostic or therapeutic methods carry mutations that lead to amino acid changes, especially in the RBD region. The World Health Organization and other authorities refer to these viruses as variants of concern or variants of interest. As of September 2021, WHO lists Alpha (UK, September 2020), Beta (South Africa, May 2020), Gamma (Brazil, November 2020), and Delta (India, October 2020) viruses as variants of concern. Also, Eta (December 2020), Iota (USA, November 2020), Kappa (India, October 2020), Lambda (Peru December, 2020) and Mu (Colombia, January 2021) mutant viruses are on he list variants of interest. In conclusion, less than 2 years of time has passed since the emergence of the COVID-19 agent SARS CoV-2 virus. However, this virus has been the most extensively studied viral agent in the history of medicine and the most detailed information has been gathered about the infection. Despite all these, it is difficult to indicate that the fight against this pathogen has been successful nor are we any closer to declare that the enormous danger the virus poses to humanity is reduced.