Novel antiviral pill for COVID-19
25 May 2021
The World Health Organization (WHO) declared the COVID-19 outbreak a pandemic on March 2020. Since then, scientists and researchers are indulged in development of vaccines for COVID-19. About 682 therapeutic candidates are now undergoing preclinical and clinical trials world-wide .Vaccines mainly aims at prevention of disease while targeted treatment is also a concern in management of disease. Remdesivir is the only approved antiviral drug for treatment of severe cases of COVID-19, and is to be administered within the hospital settings. Patients under management in home care settings take medications for symptomatic control like analgesics or antibiotics. Some patients are more prone to practice self medication and reported use of remdesivir even for minor symptoms. Hence to overcome this problem, a pill that can be taken by patient at home is being under development to be made available by end of 2021 by world’s leading pharmaceutical company Pfizer.
The new pill gives a hope to healthcare professionals and is thought to be a cure for the disease rather than prevention, reducing massive hospital admissions. Previously, combination of lopinavir and Ritonavir which are HIV protease inhibitor, failed to provide adequate response to covid treatment due to weak inhibition to 3CLpro.
Phase 1 trail of COVID-19 pill is carried out in US and Belgium. The trial is being carried out among 60 healthy volunteers of age between 18 to 60. Animal studies does not show any significant adverse effects. Phase 1 trial was double blinded, single and multiple-dose escalation study randomized, placebo controlled, evaluating safety, tolerability and pharmacokinetics of PF-07321332 and is estimated to be completed by 25th of May, 2021. It is a combined 3-part study where, part-1 is single ascending dose study. Part-2 is multiple ascending dose study and part-3 is optional relative bioavailability and food effect study. Part-1 and 2 are double blind sponsor open study and part-3 is open label cross over study.
The dug class belongs to protease inhibitor and these class of drugs are used in treatment of HIV and Hepatitis C. However, the new drug candidate is the only coronavirus specific protease inhibitor so far discovered. The new oral antiviral agent can be taken at the very early signs of Covid-19.The clinical candidate PF-07321332, is a SARS-CoV2-3CL protease inhibitor where it blocks viral replication of SARS-COV-2. Viral enzymes 3C-like protease (3CLpro), or main protease (Mpro) plays an important role in viral replication process and hence is the target for the drug candidate.
SARS-COV-2 is a single stranded RNA virus with four structural proteins. The viral genome is translated in host cell as polyproteins-pp1a and pp1ab. By proteolysis, protease enzyme of viruses is cleaved from polyproteins, and associate with papain-like protease to cleave the polyproteins to form 16 functional non-structural proteins (nsps) which helps in assembling the viral replication transcription complex (RTC) to aid in viral replication. 3CLpro is a protease enzyme of SARS act on 11 cleavage sites on the polyprotein 1ab. One of the main advantages is that, no human analog for this protease is present and hence offers less toxicity to human body. As the SARS-COV-2 is mutating, the drug can act on variants of virus.
The drug is developed as both oral and parenteral formulations, PF-07304814, is the parenteral dosage form for hospitalized patients, and PF-07321332 as a potential oral therapy agent to be taken when the patient encounter with the infection. The drug can be used alone or in combination with Remdesivir.
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