Scoping insight on antiviral drugs against COVID-19

Abstract

Background: COVID-19 is an ongoing viral pandemic produced by SARS-CoV-2. In light of in vitro efficacy, several medications were repurposed for its management. During clinical use, many of these medications produced inconsistent results or had varying limitations.

Objective: The purpose of this literature review is to explain the variable efficacy or limitations of Lopinavir/Ritonavir, Remdesivir, Hydroxychloroquine, and Favipiravir in clinical settings.

Method: A study of the literature on the pharmacodynamics (PD), pharmacokinetics (PK), safety profile, and clinical trials through academic databases using relevant search terms.

Results & discussion: The efficacy of an antiviral drug against COVID-19 is associated with its ability to achieve therapeutic concentration in the lung and intestinal tissues. This efficacy depends on the PK properties, particularly protein binding, volume of distribution, and half-life. The PK and PD of the model drugs need to be integrated to predict their limitations.

Conclusion: Current antiviral drugs have varying pharmacological constraints that may associate with limited efficacy, especially in severe COVID-19 patients, or safety concerns.

Keywords: Favipiravir; Hydroxychloroquine; Lopinavir; Pharmacodynamics; Pharmacokinetics; Remdesivir; SARS-CoV-2.

Fig. 1

Structure of RDV; the parent nucleoside analogue and final active intracellular metabolite.

Fig. 2

In vivo bioactivation pathway of RDV (Yan and Muller, 2020), In the presence of serum enzymes, the phosphate prodrugs are hydrolyzed prematurely to the nucleoside. GS-441524, which after access to the cells activated to the triphosphate. Other pathway (not shown) involves, access of RDV into the cells, its metabolism to GS-441524 monophosphate, then to GS-441524 triphosphate.

Fig. 3

RDV PK in critically ill patients after several doses of IV RDV. Left RDV, Right GS-441524 Patient 1 with renal impairment and Patient 2 without renal impairment; mean SD estimated 3–9 days after RDV initiation).

Fig. 4

Chemical structure of repurposed antiviral drugs.

Fig. 5

Total and unbound LPV median peak and trough levels in COVID −19 patients. LPV/r 400/100 mg twice daily (Gregoire et al., 2020).

Fig. 6

PK of HCQ in COVID-19. Peak level after loading dose of 200 mg TID extremely variable [0.28–0.62], mean 0.5 ug/ml. Achievement of the assumed therapeutic level [1–2 ug/ ml] was delayed (Chakraborty and Maity, 2020, Yang et al., 2020, Touret et al., 2020, Saul and Einav, 2020, Siordia et al., 2020) mean 4 days. Potentially toxic level > 2 ug/ml was observed in some patients after 5 days (Painvin et al., 2020).