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The COVID-19 virus and its Poly-proteins
Context: Structure of the Corona virus and use of drugs against it
COVID-19 is easily infecting and transmitting itself from people to people and scientists and medical experts are waging a war against its spread. Though there are treatments that can alleviate the symptoms such as difficulty breathing, they do not address the underlying cause: the virus. All over the world, experts are involved in understanding this new strain of virus and to find treatment and drug for it.
This brings us to the understanding of viruses and their structure and what can be the efforts to deal with it. In this article, we will explain the following:
- How are viruses different from bacteria?
- What is Polyprotein strategy?
- What is the structure of COVID-19?
- How the drugs work on viruses?
- What are India’s attempts in fighting the virus?
- Conclusion
How are viruses different from bacteria?
- Corona viruses do not have DNA as their genome, but RNA; in other words, they can only translate and not transcribe.
- Thus, they are ‘dead’, unable to renew and grow themselves; they need help. This they achieve by infecting ‘host cells’ which they bind to and multiply by the millions.
What is Polyprotein strategy?
- When an infection by virus occurs, entire RNA with its 33,000 bases is translated in one shot as a long tape of amino acid sequences.
- Since this long chain contains several proteins within it, it is called a “polyprotein” sequence.
- Almost all retroviruses and RNA viruses use the strategy of translating an open reading frame as a large, precursor polyprotein.
- Viruses that regulate gene expression by polyprotein processing includes several important human pathogens such as HIV, poliovirus, rhinovirus, Dengue virus, hepatitis C virus, West Nile virus, Chikungunya virus and SARS corona virus.
- Polyprotein strategy is useful to understand lifecycle of the virus and to find the relevant proteins, isolate and study what each of them does in helping infection.
- Polyproteins allow for a more compact genome by eliminating additional genetic features and express the protein when the need arises.
- Scientists call the polyprotein a ‘single reading frame’, containing several ‘open reading frames’, namely those that contain a start code and end with a stop code, each containing the relevant protein to be expressed by the host cell.
What is the structure of COVID-19?
- As per Journal of Medical Virology, COVID19 has RNA-based genomes and sub-genomes in its polyprotein sequence.
- The architecture of the virus is the spike protein (S), the membrane protein (M), the envelope protein (E), and the nucleocapsidprotein (N, which covers the viral cell nuclear material).
- There are 16 special structural and accessory proteins, called non-structural proteins (NSP), which serve specific purposes for infection and viral multiplication.
How the drugs work on viruses?
- Corona virus is made up of large set of proteins, against which a number of potential molecules and drugs can be tried to interfere and stop the production of these viral proteins.
- Remdesavir is one of several drugs being fast-tracked into trials by the World Health Organization. It is considered highly effective in stopping the replication mechanism of the corona virus that causes COVID-19. The drug targeted the key enzyme RDRp in the virus and stopped its production.
- The drug worked successfully against the Middle East Respiratory Syndrome (MERS) virus, a related corona virus.
- Other studies from the US, Germany and China have developed methods to stop the production of the enzyme (called CL3pro, also called as Mpro) which is needed to make the spike (S protein).
- According to an Indian researcher, Thanigaimalai Pillaiyar, there is no specific treatment available for human corona viruses till date, but numerous antiviral agents are being identified through a variety of approaches. His work is well known in finding drugs against SARS-CoV.
- By 3D modeling, he found a key enzyme of the SARS-CoV, called Chymotrypsin-like Cysteine Protease (3CLpro) also called the main protease (Mpro) and found that this enzyme fits into the virus structure.
- A total of about 160 known drugs were predicted to deactivate the binding of 3CLpro or pro and thus inhibit the SARS-CoV from infecting.
What are India’s attempts in fighting the virus?
- Every virus is different and so is the drugs used to treat them. SARS-CoV-2 the corona virus that causes the disease COVID-19 is completely new and attacks cells in a novel way.
- WHOlaunched a project named ‘Solidarity’, that is an international clinical trial to help find an effective treatment for COVID-19.
- The Solidarity trial will compare four treatment options against standard of care, to assess their relative effectiveness against COVID-19.
- The four most promising options include:
- an experimental antiviral compound called Remdesivir;
- the malaria medications Chloroquine and Hydroxychloroquine;
- a combination of two HIV drugs, Lopinavir and Ritonavir; and
- that same combination plus interferon-beta, an immune system messenger that can help cripple viruses.
- India will also participate in a multi-country trial to identify potential cures for the Covid-19 outbreak.
- The Central Drugs Standard Control Organization has approved the proposal of ICMR (Indian Council of Medical Research) for the clinical trial of convalescent plasma in Covid-19 patients.
- In Convalescent plasma therapy, antibodies from the blood of patients who have recovered from Covid-19 are used to treat severely infected patients.
- The Indian Council of Medical Research (ICMR) will start a new trial next week to study the efficacy of BCG vaccine in preventing Covid-19.
- Council of Science and Industrial Research (CSIR) is slated to begin clinical trials on the anti-leprosy vaccine called Mw (Mycobacterium w) to see if it can be used as a vaccine against corona virus.
- The Council of Scientific and Industrial Research (CSIR), under its New Millennium Indian Technology Leadership Initiative (NMITLI), is also seeking proposals from industries for effective containment interventions, assistive devices such as affordable ventilators, innovative diagnostics (rapid, affordable, cutting edge), novel drugs or repurposed drugs, new vaccines or repurposed vaccine and track-and-trace technologies.
- On 3 April, Department of Science & Technology (DST) has set up a ‘Centre for Augmenting WAR with COVID-19 Health Crisis’ (CAWACH)at a total cost of Rs 56 Cr to evaluate and support up to 50 innovations and start-ups that address COVID-19 challenges.
- The Government of India has set up a ‘COVID-19 Task Force’for mapping the COVID-19 related technology capabilities in start-ups, academia, research and development labs and industry. The capacity mapping group consists of representatives from DST, Department of Biotechnology (DBT), Indian Council for Medical Research (ICMR), Ministry of Electronics and Information Technology (MEIT), Council for Scientific and Industrial Research (CSIR), Atal Innovation Mission (AIM), Ministry of Micro, Small and Medium Enterprises (MSME), Startup India and All India Council for Technical Education (AICTE).
Conclusion
India is well versed with expertise in the area of organic and medicinal chemistry since the last 90 years and in manufacturing quality drug molecules and exporting them for use at home and across the world.
The Government of India is fully committed to facilitating Indian health and scientific community in the fight against COVID-19. The government scientific agencies are not leaving any stones unturned in order to provide full support to the community, researchers, private and public research labs, start-ups, incubators, entrepreneurs and industries. Funding agencies are making an effort to link national projects with global projects to share the expertise among nations, avoid duplication and speed up the entire process when and where required.
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