The Human Coronavirus Disease COVID-19: Its Origin, Characteristics, and Insights into Potential Drugs and Its Mechanisms

Abstract

The emerging coronavirus disease (COVID-19) swept across the world, affecting more than 200 countries and territories. Genomic analysis suggests that the COVID-19 virus originated in bats and transmitted to humans through unknown intermediate hosts in the Wuhan seafood market, China, in December of 2019. This virus belongs to the Betacoronavirus group, the same group of the 2003 severe acute respiratory syndrome coronavirus (SARS-CoV), and for the similarity, it was named SARS-CoV-2. Given the lack of registered clinical therapies or vaccines, many physicians and scientists are investigating previously used clinical drugs for COVID-19 treatment. In this review, we aim to provide an overview of the CoVs origin, pathogenicity, and genomic structure, with a focus on SARS-CoV-2. Besides, we summarize the recently investigated drugs that constitute an option for COVID-19 treatment.

Keywords: COVID-19; SARS-CoV-2; antiviral therapies.

Figure 1

The genomic organization of SARS-CoV-2. The genome encodes two large genes ORF1a (yellow), ORF1b (blue), which encode 16 non-structural proteins (NSP1– NSP16). These NSPs are processed to form a replication–transcription complex (RTC) that is involved in genome transcription and replication. For example, NSP3 and NSP5 encode for Papain-like protease (PLP) and 3CL-protease, respectively. Both proteins function in polypeptides cleaving and block the host innate immune response. NSP12 encodes for RNA-dependent RNA polymerase (RdRp). NSP15 encodes for RNA helicase. The structural genes encode the structural proteins, spike (S), envelope (E), membrane (M), and nucleocapsid (N), highlighted in green. The accessory proteins (shades of grey) are unique to SARS-CoV-2 in terms of number, genomic organization, sequence, and function (figure created with biorender.com).

Figure 2

The life cycle of SARS-CoV-2 in the host cells. The S glycoproteins of the virion bind to the cellular receptor angiotensin-converting enzyme 2 (ACE2) and enters target cells through an endosomal pathway. Following the entry of the virus into the host cell, the viral RNA is unveiled in the cytoplasm. ORF1a and ORF1ab are translated to produce pp1a and pp1ab polyproteins, which are cleaved by the proteases of the RTC. During replication, RTC drives the production full length (−) RNA copies of the genome and used as templates for full-length (+) RNA genomes. During transcription, a nested set of sub-genomic RNAs (sgRNAs), is produced in a manner of discontinuous transcription (fragmented transcription). Even though these sgRNAs may have several open reading frames (ORFs), only the closest ORF (to the 5′ end) will be translated. Following the production of SARS-CoV-2 structural proteins, nucleocapsids are assembled in the cytoplasm and followed by budding into the lumen of the endoplasmic reticulum (ER)–Golgi intermediate compartment. Virions are then released from the infected cell through exocytosis (figure created with biorender.com).