drug combos11 Aug 2020 11:11
This is what WHO decided to test back in January:
SARS-CoV-2 Drug Therapy
Drugs tested effective for SARS-CoV and/or MERS have been included in the WHO mega clinical trial – SOLIDARITY.31 For its study, WHO chose a nucleotide analogue Remdesivir; the malaria medication chloroquine (and its analog hydroxychloroquine); a combination of the anti-HIV drugs lopinavir and ritonavir; and that combination plus interferon-b.
Remdesivir is an antiviral prodrug of remdesivirtriphosphate with in vitro activity against coronaviruses.32,33 Remdesivir-TP acts as an inhibitor of RNA-dependent RNA polymerases and competes with adenosine-TP for incorporation into emerging viral RNA chains.34 Hydroxyhloroquine and chloroquine have in vitro activity against SARS-CoV-2 32,35 and the mechanism of action includes inhibition of viral enzymes (RNA polymerase), viral protein glycosylation, virus assembly, new virus particle transport, and virus release. Other mechanisms may also involve ACE2 receptor inhibition, decrease acidity in endosomes, and immunomodulation of cytokine release.5,32,36
The third arm of SOLIDARITY combines two HIV protease inhibitor drugs, lopinavir-ritonavir. The combination shown in vitro and in vivo potential activity for SARS-CoV and MERS-CoV 38,39 and the mechanism of action involves the inhibition of Mpro, an essential enzyme for coronavirus replication 40. Recent report published in The New England Journal of Medicine41 was not encouraging and the combination of lopinavir-ritonavir did not differ significantly from “standard care” group.
The fourth arm of SOLIDARITY combines lopinavir-ritonavir with interferon-b. The activation of innate antiviral response by interferon should have beneficial effects at least in the initial stage of infection. However, cautions should still be observed and the possibility that interferon might exacerbate inflammation during the late phase of SARS-CoV-2 infection cannot be excluded.
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