Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)  The disease was first identified in December 2019 in Wuhan, the capital of China’s Hubei province, and has since spread globally, resulting in the ongoing 2019–20 coronavirus pandemic.1,2  As of 23 April 2020, approximately 184,0003 deaths had been attributed to COVID-19.  

There are no specific antiviral medications approved for COVID-19, but development efforts are underway, including testing of existing medications. Few of these are Remdesivir, Chloroquine, Hydroxychloroquine, Lopinavir/Ritonavir.  

Nowadays drug repurposing is gaining popularity as an approach to develop new medicines. In fact, this strategy of using existing therapeutics for new indications has demonstrated success through previous observational studies. For a marketed drug, the major advantage is a faster, less risky and less costly clinical development as the approved product has already met pharmacovigilance and regulatory requirements, and undergone post market surveillance.4 

 

Ivermectin is an FDA-approved broad spectrum anti-parasitic agent5 that in recent years have shown to have anti-viral activity against a broad range of viruses6-9 in vitro. The plasma half-life of ivermectin in man is approximately 18 hours following oral administration. The causative agent of the current COVID-19 pandemic, SARS-CoV-2, is a single stranded positive sense RNA virus that is closely related to severe acute respiratory syndrome coronavirus (SARS-CoV).  

 

Studies on SARS-CoV proteins have revealed a potential role for  IMPα/β1 during infection in signal-dependent nucleocytoplasmic shutting of the SARS-CoV Nucleocapsid protein10-12, that may impact host cell division.13,14 In addition, the SARS-CoV accessory protein ORF6 has been shown to antagonize the antiviral activity of the STAT1 transcription factor by sequestering IMPα/β1 on the rough ER/Golgi membrane.15 Taken  together, these reports suggested that ivermectin’s nuclear transport inhibitory activity may be effective against SARS-CoV-2. 

To test the antiviral activity of ivermectin towards SARS-CoV-2, Leon Caly et. al.16 infected Vero/hSLAM cells with SARS-CoV-2 isolate Australia/VIC01/2020 at an MOI of 0.1 for 2 h, followed by the addition of 5 µM ivermectin. Supernatant and cell pellets were harvested at days 0-3 and analysed by RT-PCR for the replication of SARS-CoV-2 RNA.  At 24 h, there was a 93% reduction in viral RNA present in the supernatant of samples treated with ivermectin compared to the vehicle DMSO.  Similarly, a 99.8% reduction in cell-associated viral RNA was observed with ivermectin treatment. By 48h this effect increased to an ~5000-fold reduction of viral RNA in ivermectin-treated compared to control samples, indicating that ivermectin treatment resulted in the effective loss of essentially all viral material by 48 h. 

From above study it is concluded that Ivermectin is an inhibitor of the COVID-19 causative virus (SARS-CoV-2) in vitro.  Ivermectin is widely available, due to its inclusion on the WHO model list of essential medicines, and is well tolerated, hence we have proposed to study effect of Ivermectin drug on patients of COVID-19.