Hyderabad-based Laxai Life Sciences is Seeking Approval for Clinical Trial to Combat Covid-19 Pandemic: Combined Repurpose Antiviral Therapeutics

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Dr. Shuvomoy Banerjee, PhD; Neucrad Health Desk, July 13, 2020

Combined Repurpose Antiviral Therapy is going to be introduced for the prevention of novel coronavirus infections in India. In a joint venture with the Council of Scientific and Industrial Research (CSIR), Hyderabad-based Laxai Life Sciences Bio-pharma Company has sought the necessary approval from the Ministry of Science and Technology, Govt. of India for the Phase-III Clinical Trial of this particular antiviral therapy. Another important aspect of this study is Host Directed Therapy. Scientists hope that the application of host-directed therapy with combined repurpose antiviral therapy will undoubtedly add a new dimension to Covid-19 medical research.

Before discussing this topic in detail, let’s take a look at some of the essentials of antiviral therapy, repurposing antiviral drugs & host-directed therapy in detail here: 

A. Anti-viral drugs and their use:

Antiviral therapy is used as a treatment to prevent viral infections. These antivirals can be small molecule drugs, Chemical analogues, and protein inhibitors which usually prevent the infecting virus from entering into the host cell. In case, if the host cell is infected, the antiviral drug prevents viral replication by inhibiting the functional activities of its RNA polymerase enzyme. As a result, further viral propagation is prevented inside the host cell. In late 1963, the first antiviral drug, Iodoxiuridine, was approved for treatment. Several antivirals have been discovered since then, but it has been found that earlier antivirals often damage the body’s normal cells while preventing viral infections. After much research, in mid-1987, azidothymidine antiviral drug was successfully used to control HIV infection in combination with other antivirals. Due to the much advancement in medical research, many of the currently discovered antiviral drugs have been able to prevent viral infections individually or work in combinations. These include amantadine (for influenza virus), acyclovir (for herpes simplex virus), gancyclovir (for cytomegalovirus), ribavirin (for hepatitis-C virus) and so on.

B. Repurpose Antiviral Drugs:

“The most fruitful basis for the discovery of a new drug is to start with an old drug” Sir James Black

This famous quote from Sir James Black, a Nobel Prize-winning scientist in physiology and medicine in 1998, optimally suggests the idea behind the ​​repurpose antiviral drugs. While many antiviral drugs can work against multiple viruses, they may have fewer side effects on normal body cells. If no existing antivirals are known to treat the new viral infections, previously discovered antiviral drugs can be reused and checked in various combinations. The advantage of using such group of drugs is that it does not require pre-clinical trials as they are already approved and various stages of clinical trials can be studied with them easily.  These antiviral drugs can be used as “compassionate drugs” on an emergency basis. Therefore, in recent times, the use of Reapurpose antiviral drugs has become very essential tool for ‘cutting-edge’ anti-viral therapeutics.

C. Host directed therapy:

There are two main categories for antiviral treatment. 1) To stop the virus from infecting the host cell by directly attacking with antiviral drugs as well as to stop the viral replication in the infected cell.  Also, sometimes antivirals prevent the virus from making proteins by inhibiting translation process. 2) Another important aspect is to study the host factors that play a crucial role in the transmission of the virus.  In this case, antivirals are used to block the activities of those host factors by affecting their various molecular signaling pathways. In medicine, this method is called host directed therapy.

                 Of note, Laxai Life Sciences and CSIR has taken the initiative to use the repurpose antiviral drugs in three combinations which as follows:

1. Favipiravir & Colchicine
2. Umifenovir& Colchicine
3. Nafamostat & 5-ALA (5-amino livulinic acid)

The effects of drugs on Covid-19 infections and its pathology will be examined. Medanta Medcity Hospital has collaborated in the clinical trial of Combined Repurpose Antivirals. There will be trials on about 300 patients in different groups. The name of this clinical trial planned by the scientists is ‘MUCOVIN’. Director General of CSIR Dr. Shekhar C. Mande said these repurpose antiviral drugs have complementary, additive and synergistic properties. As a result, this prominent combinatorial therapy can be applied as an alternative to treat Covid-19 patients by which they recover faster. CSIR’s partners in these clinical trials are the Indian Institute of Chemical Technology in Hyderabad and the Indian Institute of Integrative Medicine in Jammu.

According to Ram S. Upadhayaya, Chief Executive Officer, Laxai Life Sciences Company stated that the proteins which help to replicate the virus will be targeted for this research specifically. Scientists will also look at some of the proteins of the host cell that are responsible for running the life cycle of SARS-CoV-2 causing ‘cytokine storms’ in the patient’s body. Mr. Vamsi Maddipatla, Managing Director of the company, emphasized the importance of this sponsorship research and stated that the company will pave the way for discovering life-saving drugs in the service of the mankind.

Undoubtedly, if this research becomes successful, a new trend will be added to the therapeutic intervention for Covid-19 infection.

References:

1. https://pib.gov.in/PressReleseDetailm.aspx?PRID=1637016
2. Yang CW, Peng TT, Hsu HY, et al. Repurposing old drugs as antiviral agents for coronaviruses [published online ahead of print, 2020 May 23]. Biomed J. 2020;S2319-4170(20)30066-4. doi:10.1016/j.bj.2020.05.003
3. https://www.cell.com/trends/microbiology/pdf/S0966-842X(18)30087-8.pdf
4. Harrison C. Coronavirus puts drug repurposing on the fast track. Nat Biotechnol. 2020;38(4):379-381. doi:10.1038/d41587-020-00003-1
5. Zumla A, Azhar EI, Arabi Y, et al. Host-directed therapies for improving poor treatment outcomes associated with the middle east respiratory syndrome coronavirus infections. Int J Infect Dis. 2015;40:71-74. doi:10.1016/j.ijid.2015.09.005
6. Zumla A, Hui DS, Azhar EI, Memish ZA, Maeurer M. Reducing mortality from 2019-nCoV: host-directed therapies should be an option. Lancet (London, England). 2020 Feb;395(10224):e35-e36. DOI: 10.1016/s0140-6736(20)30305-6.
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8. Khamaikawin W, Saoin S, Nangola S, et al. Combined Antiviral Therapy Using Designed Molecular Scaffolds Targeting Two Distinct Viral Functions, HIV-1 Genome Integration and Capsid Assembly. Mol Ther Nucleic Acids. 2015;4(8):e249. Published 2015 Aug 25. doi:10.1038/mtna.2015.22