Need for anti-viral drugs against Covid

Covid-19 is the third viral epidemic to have come upon man since the first in 2003 and it may not be the last. Next pandemic could be more destructive and there may not be an effective vaccine to fight the disease. Further developing an effective vaccine is not easy and is time consuming. By the time a vaccine is developed and tested a lot of lives may have been lost as happened in the US due to Covid-19. Adequate inoculation of a population is no easy task as could be seen at present in the African countries. Variant strains of the virus which prove to be more elusive, destructive and resistant to vaccines poses another threat. Virologists and researchers have though belatedly realized these dangers and are working hard to find solutions. Perhaps, broad spectrum antiviral drugs which are effective against viruses and their variants may be the solution.

Corona viruses have been jumping species and causing disease every nine years or so since 2003. Encroach by man into the territories of the animals is believed to be the reason for this unusual behaviour of viruses. Such encroachments deprive the wild life of their habitat and provides opportunities for invasive organisms to jump from one host to another. Sometimes these organisms prove to be pathogenic to the new host. SARS struck in 2003 and disappeared soon and everybody thought that was the end of the story. But people like Robert Webster leading authority on avian influenza warned against complacence and advised researchers to prepare for the next outbreak. He recommended drugs that target a wide range of viral pathogens should be developed and stockpiled. Drug researchers did not listen to him and the industries that fund research were not interested as there was no disease they could see. They will not fund research unless they are assured of profits.

Another warning shot came in 2012. Middle East Respiratory Syndrome or MERS appeared and disappeared. There was still no concerted effort to develop vaccines or drugs. In 2020 all hell broke lose. SARS Cov-2 struck with a vengeance and Covid-19 engulfed the world. There was a mad rush to develop a vaccine and the researchers were successful in producing several excellent vaccines. But the virus seems to be having other ideas, it produced several variants with increasing infectiousness and also to some degree vaccine resistance. And the virus is not done yet. Only god knows what kind of monster it may produce next.

The need for an anti-viral drug was felt from the beginning of the pandemic as doctors felt unarmed against an enemy with the ability to improve its weapons and change its strategies. They tried the drug remdesivir which had been developed in the fight against hepatitis C and Ebola. This drug was of little use against Covid and had other disadvantages like the cost and the fact that it has to be given intravenously, factors that make the drug almost useless in pandemic situations.

Anti-viral drugs are difficult to develop for in the virus there are only a few structures that could be targeted by drugs. In the case of other pathogens like bacteria, fungi and parasites there are several anatomical and chemical areas that a drug could attack successfully and make the organism ineffective in causing disease. In enveloped viruses there are only the lipid envelop, few proteins and the genetic core material. The surface cell membrane in bacteria on the other hand is a common structure found in many bacteria and a drug like penicillin which inhibits the formation of the cell membrane could be effective against a large number of different types of bacteria. Therefore the researchers say “now we need an arsenal” as no single drug could be effectiive against all the emerging pathogenic viruses.

Realising the immense danger paused by Covid and similar infections that may occur in the future the National Institute of Health in the US is planning a major programme to develop therapeutics against SARS Cov-2 variants and other viruses with pandemic potential. The project would not be starting from scratch as several initial efforts for developing suitable drugs have been made and strategies developed with some success from the beginning of the present pandemic. Scientists have been saying “we don’t want to have another year like 2020 and we don’t have to if we do the work in advance”. The investment made in the field of molecular biology research and virology in the last couple of decades would no doubt stand in good stead in this endevour.

Basically, two strategies are being developed, one is to target the virus physiology and the other is to target the mechanisms in the human physiology that the viruses commandeer for their own purpose. Drugs could function as fake building blocks for the virus and mislead the virus to use them for replication which would fail as wrong building blocks have been made available. Instead of inserting the correct RNA bases during replication a viral enzyme called polymerase is tricked into incorporating derivatives of the drug. Human polymerases cannot be similarly misled and therefore human physiology remains unharmed. But because of the limited targets in the viral structure a drug effective against herpes is unlikely to be effective against Corona.

Some drug researchers as mentioned earlier aim to interfere with human pathways that viruses hijack for their replication, for example a drug that blocks fat-regulating enzyme used by many viruses to promote entry into host cells could stop its entry into human cells. By inhibiting this enzyme the virus is deprived of access to host function upon which it depends for its invasive process. Another host directed antiviral strategy is to deprive the virus the lipids that it steals from human cells to manufacture its lipid envelope without which it cannot exist. As everybody now knows soap causes disintegration of this wrapping of fat and that is why we are told to wash our hands as often as possible as a Covid preventive measure.

All this great effort has resulted in the production of a promising candidate drug called molnupiravir which is easier to assimilate and therefore is cheaper and could be administered orally and therefore very practical in pandemic situations. This drug is now undergoing late stage clinical trials and is nearing approval. It is found to shorten the duration of the infectiousness of Covid. This drug targets the Corona virus and provides it with fake building blocks for the replication process of its RNA genome.

We must realise that only science could save us from monsters like the Covid. Superstitious mumbo jumbo has no place in a life threatening situation like this. We have to look up to the West who are ahead in science and technology in this area though the East is not far behind. We hear good news from China too in the battle against Corona and they are expected to unveil their anti-viral drugs sooner than later. Sri Lanka which maintains good relations with both West and East could benefit in this situation for if one fails the other would surely oblige.

N.A.de S. Amaratunga