Pre-clinical data:
Therapeutic efficacy was first demonstrated by suppressing viral
replication in Ebola infected infected rhesus monkeys. Prophylactic use
was initiated 24 h prior to viral challenge, whereas therapeutic use was
initiated 12 h after challenge. The severity of pulmonary infiltrates,
were significantly better in the prophylactic and therapeutic groups,
comparing each to controls.[4] Efficacy studies in
Ces1c−/− mice demonstrated therapeutic efficacy of this drug against
Severe Acute Respiratory Syndrome (SARS)-CoV and Middle East Respiratory
Syndrome coronavirus (MERS-CoV). Sheahan et al. found that both
prophylactic and therapeutic remdesivir had protective effects against
MERS-CoV replication and associated pathology, generally resulting in
less lung damage and better pulmonary function.[5] In 2018, Murphy et al. examined the efficacy
of this drug against Feline infectious peritonitis (FIP) in 12
experimentally infected cats. In the 10 infected cats, treatment was
initiated ( 5 cats with 5mg/kg daily and 5 cats with 2mg.kg daily) upon
onset of FIP-associated clinical signs and continued for 2 weeks. All
treated cats demonstrated favorable responses to remdesivir treatment
within 24–48 h.[6] Pedersen et al. treated 31
cats with an initial dose of 2 mg/kg daily. A total of 25 treated cats
(81%) survived FIP for at least 44 weeks of follow up, indicating that
this drug is also a promising therapeutic candidate for treatment of
alphacoronavirus- related disease in cats. This study was done on cats
with naturally occurring CoV infection, representing real world
situation.[7] Efficacy of this drug was also
tested against Nipah virus Bangladesh genotype among African green
monkeys and it showed all remsdesivir-treated animals survived and mild
respiratory signs were observed in two out of four treated
animals.[8] It also exhibited antiviral activity
in vitro against other virues like Marburg virus,Paramyxoviridae (such
as parainfluenza type 3 virus, Nipah virus, Hendra virus, and measles
and mumps viruses) and Pneumoviridae (such as respiratory syncytial
virus).[9] Wuhan Virus Research Institute carried
out a vitro inhibition test and found that remdesivir can block virus
infection at very low micromolar concentration of Vero E6 cells infected
with virus, and the cell selectivity is high (EC50 = 0.77 μM, CC50
> 100 μM, SI > 129.87). It draws a speculation
that it could also play a role (EC90 =1.76 μΜ) in SARS-CoV-2 infected
monkeys.[10] Preclinical studies are compiled in
Table 1.