The novel coronavirus Disease-2019 (COVID-19): Mechanism of action, detection and recent therapeutic strategies

Abstract

Novel coronavirus SARS-CoV-2, designated as COVID-19 by the World Health Organization (WHO) on the February 11, 2020, is one of the highly pathogenic β-coronaviruses which infects human. Early diagnosis of COVID-19 is the most critical step to treat infection. The diagnostic tools are generally molecular methods, serology and viral culture. Recently CRISPR-based method has been investigated to diagnose and treat coronavirus infection. The emergence of 2019-nCoV during the influenza season, has led to the extensive use of antibiotics and neuraminidase enzyme inhibitors, taken orally and intravenously. Currently, antiviral inhibitors of SARS and MERS spike proteins, neuraminidase inhibitors, anti-inflammatory drugs and EK1 peptide are the available therapeutic options for SARS-CoV-2 infected individuals. In addition, Chloroquine, which was previously used for malarial and autoimmune disease, has shown efficacy in the 2019-nCoV infection treatment. In severe hypoxaemia, a combination of antibiotics, α-interferon, lopinavir and mechanical ventilation can effectively mitigate the symptoms. Comprehensive knowledge on the innate and adaptive immune responses, will make it possible to propose potent antiviral drugs with their effective therapeutic measures for the prevention of viral infection. This therapeutic strategy will help patients worldwide to protect themselves against severe and fatal viral infections, that potentially can evolve and develop drug resistance, and to reduce mortality rates.

Keywords: Coronavirus; Immune response; Pathogen; Respiratory syndrome; Treatment.

Graphical abstract

Fig. 1

Coronavirus structure. Coronaviruses are enveloped, non-segmented virus with a positive‐sense single‐stranded RNA and phosphorylated nucleocapsid (N) protein.

Fig. 2

Phylogenetic analysis of whole genomes of SARS-CoV 2 and Pangolin-CoV, SARS-CoV, MERS-CoV and Bat-CoV).

Fig. 3

Fellow diagram for COVID-19 confirmation.

Fig. 4

After coronavirus infection, macrophages are activated and antigen-presenting cells (APC) display antigen to T cells. In cellular immunity, CD4 and CD8 with T cells produce cytokines to suppress the virus. T cells affect T helper cells to secrete interferons and interleukins. On the other hand, humoral immunity Th-2 activates B cells to produce memory B cells and antibodies. CoV attaches to DPP4R in the host cell through the S protein, causing genomic RNA to enter the cytoplasm. When CoV replicates, infected cell can partially start an immune response against dsRNA. The cascade of dsRNA and signaling pathways (IRF and NF-κB activation, respectively) sensitizes TLR-3 and is activated to produce type I IFN and proinflammatory cytokines. Type I IFN production plays a major role in increasing the release of antiviral proteins to protect uninfected cells.