Emerging pharmacotherapies for COVID-19

Abstract

Novel Corona-virus Disease 2019 (nCOVID 19) is caused by a novel virulent corona virus and leads to potentially fatal virulent pneumonia and severe respiratory distress syndrome. It was initially declared as public health emergency if international concern by WHO followed by Pandemic on 12th March 2020. As of 10th April 2020, more than 1.5 million people are affected globally with around 95,000 deaths. Vaccines for this deadly virus are currently under development and many drugs used for other indications have been repurposed and investigated for prophylaxis and treatment of COVID 19. As per SOLIDARITY trial by WHO, some of the most promising candidates include chloroquine phosphate and hydroxychloroquine which are anti-malarial medications, Remdesivir, Lopinavir-Ritonavir combination with or without interferon which are anti-HIV drugs and convalescent plasma therapy. The current evidence of efficacy and ongoing research has been elaborated in the article. Besides, there has been evidence regarding inflammatory pathogenesis of this virus leading to cytokine storm in susceptible individuals. Thus, anti-proinflammatory cytokine drugs like Anakinra and Tocilizumab are undergoing multiple trials and some results are encouraging. Similarly, use of anti-inflammatory cytokines like IL-37 and IL-38 is hypothesised to be useful and is under research. The situation is still evolving and hence there is yet no definitive therapy but to conclude the use of repurposed medications can be a boon till a definitive therapy and vaccines are developed.

Keywords: Chloroquine; Hydroxychloroquine; Remdesivir.

Graphical abstract

Fig. 1

Commonly observed signs and symptoms in COVID 19 infection (As shown in Fig. 1, three most common symptoms are fever, dry cough and fatigue followed by other symptoms like anosmia, and headache.

Fig. 2

Diagrammatic representation of the structure of novel corona virus.

Fig. 3

Experimental therapeutic strategies attempt to interfere with different steps in the coronavirus replication cycle. (It shows various targets for potential drugs. Hydroxychloroquine and chloroquine prevent entry into the cell, convalescent plasma is responsible for passive immunity while all the anti-viral drugs and protease inhibitors like Lopinavir are responsible for inhibiting viral replication and processing of viral proteins. Not shown in the figure are various pro-inflammatory cytokines like IL-1 responsible for increased fatality through cytokine storm.