There are at least 50 different drugs, from HIV protease inhibitors to antivirals to ACE inhibitors, anti-inflammatory, pneumonia, respiratory tract, malaria, tuberculosis, gout, leprosy, alcohol dependence, immunomodulators and anti-diarrhea being tested.
But the Indian Council for Medical Research has approved a Lopinavir-Ritonavir fixed dose combination (FDC), originally prescribed for the treatment of HIV / AIDS, for Covid-19 patients. Clinical studies in the field of drug reuse and FDC involve testing the optimal dose in a limited number of patient cohorts. When time is of the essence, drug dosage and efficacy as well as side effects are clearly known for recycled drugs. These drugs also offer the benefit of being typically off-patent (the older ones) and are already manufactured by Indian generic pharmaceutical companies. Task Force for Repurposing of Drugs ranked Favipiravir and Tocilizumab as the most promising to fight the disease.
The fresh arrival to the treatment area is Remdesivir, an RNA polymerase inhibitor; it stops coronavirus from replication. Gilead SciencesThe United States discovered Remdesivir to fight the outbreak of the Africa Ebola virus in 2014. It has now resurfaced this molecule through an accelerated clinical trial of solidarity.
Gilead owns the patent rights of Remdesivir, granted by the Indian Patent Office on February 18 this year. The manufacture and sale of Remedesivir requires the negotiation of conditions between Indian pharmaceutical companies and Gilead. Important observations made by US National Institute of Allergy and Infectious Diseases (NIAID) and the US Food and Drug Administration (US-FDA) are that Remdesivir can shorten recovery from 15 days to 11 and improve mortality from 11.6% to 8%. Remdesivir is administered intravenously, which means that patients will have to be in the hospital.
Favipiravir is a purinucleic acid analog and potent RNA-dependent RNA polymerase inhibitor approved for use in influenza. Both “virs” work by a similar RNA virus cell disruption mechanism. A few Indian companies have been granted clinical trials with Favipiravir, including the Council for Scientific and Industrial Research (CSIR).
Published results from a clinical study with Favipiravir show that out of 80 patients, 35 who received the drug demonstrated significantly shorter viral clearance time compared to 45 in the control arm (those who did not) – with a median recovery of four days with 11 .The 7-day clinical recovery rate also increased from 55.86% to 71.43% in the drug arm.
Favipiravir is a bioavailable pill marketed as Avigan by Fujifilm in Japan. Patents were filed in India around the year 2000 and its manufacturing process for economic production is largely in place. The molecular complexity of Remdesivir (formula: C27 H35 N6 O8 P) together with the chirality of the molecule or single-handed ability means that its synthesis and manufacturing process will be a greater challenge and at a higher cost than Favipiravir (C5 H4 F N3O2). Remdesivir is a new drug with its synthetic route and upscaling un optimized as it is today.
Favipiravir may be an affordable COVID-19 drug subject to a favorable outcome in human clinical trials.
The author is Director, CSIR-National Chemical Laboratory, Pune, and a Senior Professor of Chemistry, Hyderabad Central University. The views are personal