Rifampicin for COVID-19

Table 1 Studies on the possible antiviral properties of rifampicin against severe acute respiratory syndrome coronavirus 2

Ref.	Year	Findings
Becker[10]	1976	Rifampicin belongs to the rifamycins, characterized as antiviral drugs which inhibit transformation of cells by viruses
[24]	1969	Rifampicin has a direct antiviral effect in mammalian viruses as poxviruses including the causative agent of smallpox and on viruses which have their own RNA polymerase
Campbell et al[27]	2001	The inhibition mechanism of rifampicin to the RNA polymerases is a simple steric block of transcription elongation due to its ability to bind tightly to non-conserved parts of the structure, disrupting a critical RNA polymerase function
Ben-Ishai et al[28], Moss et al[29], McAuslan et al[30]	1969	Rifampicin inhibits the late viral protein synthesis, the virion assembly, and the viral polymerase itself
Moshkowitz et al[31]	1971	Rifampicin’s antiviral effect is dependent on the administration route, with local application resulting in higher concentrations at the site of viral replication
Tewes et al[32]	2008	Administration of rifampicin by nebulization is possible using aerosolized rifampicin-loaded polymeric microspheres
And et al[36]	1980	Intracellular rifampicin concentrations exhibit effective antiviral activity against: Influenza virus A, African swine fever virus and cytomegalovirus
Dardiri et al[37]	1971
Halsted et al[38]	1972

Table 2 In silico studies indicating rifampicin’s possible effectiveness against coronavirus disease-2019

Ref.	Year	Findings
Mishra et al[39]	2020	Using a computer-aided drug designing approach, rifampicin was the most promising existing drug that could be repurposed for the treatment of COVID-19
Parvez et al[40]	2020	Using a comprehensive drug repurposing and molecular docking approach, prediction of potential inhibitors for RNA-dependent RNA polymerase of SARS-CoV-2 revealed that rifabutin could be an effective drug for COVID-19, having the lowest binding energy compared to the positive control remdesivir
Forrest et al[41]	2010	Rifabutin belongs to the rifamycins (rifampicin, rifapentine and rifabutin); rifampicin is the most used
Pokhrel et al[42]	2020	In silico virtual screen within the United States Food and Drug Administration-approved drugs targeting the RNA-dependent RNA polymerase, which is the critical enzyme for coronavirus replication, placed rifampicin among the five most potent potential anti-SARS-CoV-2 therapeutics
Pathak et al[43]	2021	A similar approach, by targeting the main protease of SARS-CoV-2 but also TNF-α, IL-6, IL-1β, revealed rifampicin as one of the most promising drugs
Elkarhat et al[44]	2020	The SARS-CoV-2 RNA dependent RNA polymerase (nsp12) catalyzes the replication of RNA from RNA templates. Changes in the virus life cycle are exhibited by the fixation of specific ligands in the active site of this crucial enzyme. A recent study found the highly conserved nsp12 motifs, and discovered the interactions with rifabutin and rifampicin, concluding that both could function as inhibitors of the SARS-CoV-2 nsp12 protein
Soni et al[45]	2020	An in silico docking approach also found that rifampicin has good binding affinity with the COVID-19 protease, proposing its use as therapeutic treatment as well as prophylaxis

COVID-19: Coronavirus disease-2019; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2.