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Review
. 2021 Oct;39(17):6828-6841.
doi: 10.1080/07391102.2020.1802345. Epub 2020 Aug 5.

Current status and strategic possibilities on potential use of combinational drug therapy against COVID-19 caused by SARS-CoV-2

Arif Jamal Siddiqui  1 , Sadaf Jahan  2 , Syed Amir Ashraf  3 , Mousa Alreshidi  1 , Mohammad Saquib Ashraf  4 , Mitesh Patel  5 , Mejdi Snoussi  1   6 , Ritu Singh  7 , Mohd Adnan  1
Affiliations
Review

Current status and strategic possibilities on potential use of combinational drug therapy against COVID-19 caused by SARS-CoV-2

Arif Jamal Siddiqui et al. J Biomol Struct Dyn. 2021 Oct.

Abstract

The spread of new coronavirus infection starting December 2019 as novel SARS-CoV-2, identified as the causing agent of COVID-19, has affected all over the world and been declared as pandemic. Approximately, more than 8,807,398 confirmed cases of COVID-19 infection and 464,483 deaths have been reported globally till the end of 21 June 2020. Until now, there is no specific drug therapy or vaccine available for the treatment of COVID-19. However, some potential antimalarial drugs like hydroxychloroquine and azithromycin, antifilarial drug ivermectin and antiviral drugs have been tested by many research groups worldwide for their possible effect against the COVID-19. Hydroxychloroquine and ivermectin have been identified to act by creating the acidic condition in cells and inhibiting the importin (IMPα/β1) mediated viral import. There is a possibility that some other antimalarial drugs/antibiotics in combination with immunomodulators may help in combatting this pandemic disease. Therefore, this review focuses on the current use of various drugs as single agents (hydroxychloroquine, ivermectin, azithromycin, favipiravir, remdesivir, umifenovir, teicoplanin, nitazoxanide, doxycycline, and dexamethasone) or in combinations with immunomodulators additionally. Furthermore, possible mode of action, efficacy and current stage of clinical trials of various drug combinations against COVID-19 disease has also been discussed in detail.Communicated by Ramaswamy H. Sarma.

Keywords: ACE2 receptor; COVID-19; Coronavirus; SARS-CoV-2; immunomodulators.

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Conflict of interest statement

The authors have declared no conflict of interest.

Figures

Figure 1.
Figure 1.
Pictorial world map representation of continent wise total number of cases and deaths with top affected countries until 21st June 2020. Data retrieved from (ECDC 2020).
Figure 2.
Figure 2.
Diagrammatic representation of the MERS-CoV, SARS-CoV-1 and SARS-CoV-2 spread by coughing, and the possible effective drugs used against these viruses. During infection lungs alveoli get damaged, and the possible drugs can reverse the damage and restore the normal functioning of the lungs.
Figure 3.
Figure 3.
Model depicting the proposed drugs (hydroxychloroquine, azithromycin, ivermectin, favipiravir, remdesivir) with their possible acting points and mechanism* against SARS-CoV-2. *SARS-CoV-2 enters the human cell and initiate its replication cycle. First stage starts with the binding of SARS-CoV-2 virus with ACE2 receptor, followed by transfer of viral RNA in to the human cell. RNA-dependent RNA polymerase (RdRp) enzyme initiates the production of viral RNAs. During RNA methylation, RNA cap is formed, which protects against the innate immune responses. Furthermore, during the process of viral RNA synthesis, translation of proteins is associated with pH-dependent membrane stress, which possibly elicits adverse effects against immune cells and cytokines. During this stage, if the viral replication cycle is not inhibited or infected cells are not eradicated; packed/assembled viruses will get disseminated and transfect other healthy host cells.
See this image and copyright information in PMC

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