J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website http://www.jocmr.org

Review

Volume 12, Number 8, August 2020, pages 463-471

Exploring Repurposing Potential of Existing Drugs in the Management of COVID-19 Epidemic: A Critical Review

Figure 1. PRISMA diagram showing literature search and stepwise derivation to eligible papers. PRISMA: preferred reporting items for systematic reviews and meta-analyses.

**Table 1.** Distribution of 22 Studies Under Assessment, Both Drug Wise and Study Design Wise
Drugs/therapy	Study design	Total
HCQ: hydroxychloroquine; CQ: chloroquine.
HCQ/CQ with macrolide (azithromycin/clarithromycin)	1		1	1	3
HCQ	2	1		2	5
Lopinavir/ritonavir	1		1	2	4
Umifenovir/favipiravir	1				1
Methylprednisolone (with other agent)		1	1		2
Thalidomide with methylprednisolone			1		1
Remdesivir	2			1	3
Interferon (in combination)	1	1		1	3
Total	8	3	4	7	22

Table 1. Distribution of 22 Studies Under Assessment, Both Drug Wise and Study Design Wise

Drugs/therapy

Study design

Total

Clinical trial

Case series

Case report

Observational study

HCQ: hydroxychloroquine; CQ: chloroquine.

HCQ/CQ with macrolide (azithromycin/clarithromycin)

HCQ

Lopinavir/ritonavir

Umifenovir/favipiravir

Methylprednisolone (with other agent)

Thalidomide with methylprednisolone

Remdesivir

Interferon (in combination)

Total

**Table 2.** Mechanism of Action of Drug Candidates on SARS-CoV-2 Infection
Drugs	Types	Mechanism of action
SARS-CoV-2: severe acute respiratory syndrome coronavirus 2.
Chloroquine and hydroxychloroquine	4-aminoquinoline	The post-translation alteration of newly synthesized proteins via glycosylation inhibition [52].
Lopinavir/ritonavir	Protease inhibitors	Blocks viral cellular entry [53].
Umifenovir	Fusion inhibitor	Viral fusion inhibition with the targeted membrane, which blocks virus entry into the cell [54].
Favipiravir	RNA polymerase inhibitors	Favipiravir is a prodrug that is ribosylated and phosphorylated intracellularly to form the active metabolite favipiravir ibofuranosyl-5’-triphosphate (T-705-RTP). T-705-RTP competes with purine nucleosides and interferes with viral replication by incorporation into the virus RNA and thus, potentially inhibiting the RNA-dependent RNA polymerase (RdRP) of RNA viruses [31].
Methylprednisolone	Corticosteroids	Prolongs the survival time and prevents complication of clinical cases through its anti-inflammatory and immunomodulatory action [55].
Thalidomide	Immunomodulators	It has an anti-inflammatory action due to its ability to speed up the degradation of messenger RNA in blood cells and thus reduce tumor necrosis factor-α (TNF-α). Furthermore, thalidomide can increase the secretion of interleukins (IL), such as IL-12, and activate natural killer cells [56].
Remdesivir	Adenosine nucleotide analogues	Remdesivir’s ability is to metabolize into an active form known as GS-441524 which is an adenosine nucleotide analog. The GS-441524 interferes with the action of viral RdRP and evades proofreading by viral exoribonuclease (ExoN). This decreases viral RNA production [37].
Interferon	Low molecular weight protein	The expression of the interferon-stimulated genes (ISGs) is induced by interferon, in the infected as well as in neighboring cells. These lead to development of an antiviral environment, thus inhibiting further viral replication. The interferons augment the immune system in various ways, resulting in different antiviral, antiproliferative and immunomodulatory activities [48-50].

Table 2. Mechanism of Action of Drug Candidates on SARS-CoV-2 Infection

Drugs

Types

Mechanism of action

SARS-CoV-2: severe acute respiratory syndrome coronavirus 2.

Chloroquine and hydroxychloroquine

4-aminoquinoline

The post-translation alteration of newly synthesized proteins via glycosylation inhibition [52].

Lopinavir/ritonavir

Protease inhibitors

Blocks viral cellular entry [53].

Umifenovir

Fusion inhibitor

Viral fusion inhibition with the targeted membrane, which blocks virus entry into the cell [54].

Favipiravir

RNA polymerase inhibitors

Favipiravir is a prodrug that is ribosylated and phosphorylated intracellularly to form the active metabolite favipiravir ibofuranosyl-5’-triphosphate (T-705-RTP). T-705-RTP competes with purine nucleosides and interferes with viral replication by incorporation into the virus RNA and thus, potentially inhibiting the RNA-dependent RNA polymerase (RdRP) of RNA viruses [31].

Methylprednisolone

Corticosteroids

Prolongs the survival time and prevents complication of clinical cases through its anti-inflammatory and immunomodulatory action [55].

Thalidomide

Immunomodulators

It has an anti-inflammatory action due to its ability to speed up the degradation of messenger RNA in blood cells and thus reduce tumor necrosis factor-α (TNF-α). Furthermore, thalidomide can increase the secretion of interleukins (IL), such as IL-12, and activate natural killer cells [56].

Remdesivir

Adenosine nucleotide analogues

Remdesivir’s ability is to metabolize into an active form known as GS-441524 which is an adenosine nucleotide analog. The GS-441524 interferes with the action of viral RdRP and evades proofreading by viral exoribonuclease (ExoN). This decreases viral RNA production [37].

Interferon

Low molecular weight protein

The expression of the interferon-stimulated genes (ISGs) is induced by interferon, in the infected as well as in neighboring cells. These lead to development of an antiviral environment, thus inhibiting further viral replication. The interferons augment the immune system in various ways, resulting in different antiviral, antiproliferative and immunomodulatory activities [48-50].