The current understanding and potential therapeutic options to combat COVID-19

Abstract

The ongoing wreaking global outbreak of the novel human beta coronavirus (CoV) pathogen was presumed to be from a seafood wholesale market in Wuhan, China, belongs to the Coronaviridae family in the Nidovirales order. The virus is highly contagious with potential human-human transmission which was named as the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has spread across six continents and emerged as a global pandemic in short span with alarming levels of spread and severity. This virus associated symptoms and infectious respiratory illness is designated as coronavirus disease 19 (COVID-19). The SARS-CoV-2 possesses enveloped club-like spike protein projections with positive-sense large RNA genome and has a unique replication strategy. This virus was believed to have zoonotic origin with genetical identity to bat and pangolin CoV. In the current review, we introduce a general overview about the human CoVs and the associated diseases, the origin, structure, replication and key clinical events that occur in the COVID-19 pathogenicity. Furthermore, we focused on possible therapeutic options such as repurposing drugs including antimalarials, antivirals, antiparasitic drugs, and anti-HIV drugs, as well as monoclonal antibodies, vaccines as potential treatment options. Also we have summarized the latest research progress on the usage of stem cell therapy, human convalescent serum, interferon's, in the treatment of COVID-19.

Keywords: COVID-19; Repurposing drugs; SARS-CoV-2; Spike proteins; Zoonotic origin.

Graphical abstract

Fig. 1

Structure of human SARS-CoV-2.

Fig. 2

Genome of SARS CoV-2. The virion contains a single positive-sense RNA genome with a total of ~30,000 nucleotides (nt). The genome includes a 5′-cap, 5′-untranslated region (UTR), a large number of transcripts encoding 10 open reading frames(ORFs), ORFs with fusion, deletion, and/or frameshift and 3′-UTR, the essential genes that make complete viral genome from 5′ to 3′ are as follows 1) ORF1ab that encodes replicase polyprotein 1a and 1b, the ORFs 2–10 encodes viral structural proteins which include spike (S), envelope (E), membrane (M), nucleocapsid (N) and other accessory proteins. The ORF1ab gene constitutes a total of 16 non-structural proteins (NSPs1–16) within the pp1ab gene.

Fig. 3

The life cycle of SARS-CoV-2 in human host cells; begins its life cycle when spike protein binds to the angiotensin converting enzyme 2 (ACE-2) present on the outer surface of the cells in lungs, arteries, heart, kidney, and intestines. SARS-CoV-2 also enters the cells via pH dependent endocytosis. The newly formed viral particles will be transported outside by exocytosis.