1.2 Ribavirin
SARS-CoV-2, a single-stranded RNA beta coronavirus, reproduces itself by
utilizing enzymes such as 3-chymotrypsin-like protease, papain-like
protease, helicase, and RNA-dependent RNA polymerase. The potential
therapy against SARS-CoV-2 may target to its virus structure. For
instance, a study reported that nucleoside analogs are effective against
HIV and respiratory viruses by targeting the viral RNA polymerase (Li &
De Clercq, 2020). Owing to the similarity of structure between
SARS-CoV-2 and HIV or respiratory virus, nucleoside analogues may have a
therapeutic role by blocking RNA synthesis in SARS-CoV-2. Ribavirin, a
guanine analog, showed activity against other coronaviruses, showing
itself as a suitable candidate for COVID-19 treatment. A clinical study
on SARS revealed that 126 SARS-CoV patients on ribavirin treatment,
presented with hemolysis and anemia in up to 76% and 49% of the cases,
respectively (Booth et al., 2003; Tan et al., 2004). And in vivostudy demonstrated that the serum concentrations of ribavirin, inhibited
viral replication effectively, surpassed the safe human concentration
(Tan et al., 2004). In vitro data suggests that ribavirin
monotherapy confers rapid resistance for SARS and MERS, whereas the
combination therapy with Lopinavir/ritonavir or chloroquine analogs
showed potential activity (”[Expert consensus on chloroquine phosphate
for the treatment of novel coronavirus pneumonia],” 2020; Falzarano et
al., 2013).
The therapeutic regimen of ribavirin is 500 mg twice/thrice in a day
combined with Lopinavir/ritonavir or IFN-α, based on the Treatment Plan
Revised Edition 5 from China (” Treatment Plan Edition 5 revision
edition,” 2020). Although this information may be updated as new
evidence becomes available, previous experience in SARS and MERS can
provide an appropriate direction for enhancing the efficacy of
ribavirin. An in vitro study demonstrated antiviral activity against the
WIV04 strain of SARS-CoV (M. Wang et al., 2020). There is no sufficient
data on clinical trials for ribavirin, thus its efficacy may be
speculated from the experience against MERS and SARS.
The most commonest adverse effect of ribavirin is hemolytic anemia,
which occurred in up to 61% of the patients in a study assessing its
adverse effects in the treatment of SARS (Knowles, Phillips, Dresser, &
Matukas, 2003). Hemolytic anemia occurs within 3-5 days after high
loading doses (> 1-2 g) against coronavirus infection (C.
H. Chang, Chen, Lai, & Chan, 2002; Chu et al., 2004). Ribavirin is
eliminated primarily through renal excretion; it is important to effect
strict dose reductions that vary based on the indication, for patients
with renal insufficiency. Ribavirin has teratogenic potential and is
contraindicated in pregnancy and male partners of pregnancy (Altınbas,
Holmes, & Altınbas, 2020).
The evidence from the treatment of ribavirin against other coronaviruses
suggests limited efficacy and potential toxicity, which indicates that
its therapy in patients with COVID-19 should be considered as
combination therapy for enhancing the clinical efficacy.