Corona battle: We can win only with community driven approach

The present SARS-CoV 2 (COVID 19) was predicted by virologists in 2007 after the Cat SARS-CoV pandemic zoonotically spread by civet cats in 2003. Past scientific studies of SARS virus will be useful now to prevent and control coronavirus and to plan for a healthcare strategy.

In 2003, SARS-CoV pandemic broke out in China and 8,000 people were affected with fatality rate of 10 % in 30 countries. The SARS-CoV of 2003 year originated from civet cats in the meat markets of China. In the Chinese wet meat markets, live wild animals, civet cats, bats and other animals kept were in overcrowded cages. The animals were butchered and sold into fresh meat as per the choice of customers. The zoonotic spread of the SARS coronavirus was attributed to civet cat and then spread human to human. Now it appears is the turn of horseshoe bat in Wuhan meat market for this present novel coronavirus to take a zoonotic jump to cause the scientifically called SARS-CoV2. However, the present Covid-19 originated from bats requires confirmation. In fact, under the family of SARS-CoV there are 36 coronaviruses. All these viruses cause respiratory (cough, cold and lung infection) or intestinal infections in humans and animals.

At the time of SARS of 2003, there was not enough knowledge or experience to control the infection in hospitals and International travel accelerated the spread of the pandemic. Subsequently, based on scientific, clinical and other experiences of SARS 2003, there

were many predictions about the occurrence of a similar outbreak. The SARS-CoV (Covid-19) that made a zoonotic jump from horseshoe bat was indeed startlingly predicted in several scientific articles. The articles point out the fact that the bats being reservoirs of viruses can spread infections if the situation and conditions are favourable for the induction, amplification and transmission of viruses can happen very easily. To our consternation, it happened now in 2020 after a gap of 17 years.

There is a plethora of scientific studies on coronaviruses that has been documented and published. The novel coronavirus isolated from bats in negatively stained electron microscopy revealed particles of 80-140 nm as per images in the scientific journals. The virus reveals a projection of surface proteins appears as spikes from the lipid envelope. This characteristic projections/ images of novel coronavirus engulfed in lipids and proteins were well known to us now, thanks to the newspapers and media.

Let's make a little analysis of SARS-CoV. The SARS coronavirus has high degree of stability in the environment as spreads as droplets. It can survive two to three days on surface. Further generally coronaviruses are enveloped in positive sense single standard RNA viruses, genome size of 30 Kb. Analysis of genome sequences of many isolates of coronaviruses including SARS-CoV and the present SARS-CoV2 (isolated from infected BAT) revealed some similarities and some variables, among them the most conserved region "orfb" of genome is generally chosen as design for clinical diagnostic tests. Some of the salient features highlighted in the scientific papers include the following. The laboratory diagnostic kits for coronaviruses include nucleic acid amplification assay, antigen detection assay and antibody detection assay diagnostic tests, choosing antiviral drugs and vaccines may be selected /designed on the basis of understanding genome structure and function of various viral proteins involved in the life circle of these viruses. To, a limited extent some preliminary gene sequence seems to be done on this bat Coronavirus (COVID-19).

Clinical side, as per the scientific literature, to treat 2003 SARS coronavirus, the antivirals including ribavirin, ritonavir, corticosteroids, methylpredinisolone were tried. The results are not conclusively clear as to which one is better. In animals and in vitro tests protease inhibitors like Nelfinavir, Indomethacin, Chloroquine, small interfering RNA (SiRNA), Ribavirin, Lopinavir demonstrated activity in reducing replication and viral protein expression. Perhaps this treatment may cure COVID-19, However, this treatment depends on practical experience of the doctors.

Remdesivir, a nucleoside analogue and antiviral drug was developed for Ebola virus and is now being studied in Phase III clinical trials against Covid-9 as for scientific report. Depending on availability and desirability, antiviral drugs that are available for HIV/AIDs may be considered by doctors to treat Covid-19. The drugs that are used in 2003 SARS coronavirus, the antivirals including ribavirin, ritonavir, corticosteroids, methylpredinisolone may be tried. Those antiviral and protease inhibitors which include chloroquine should be tried, but it appeared the doctors in India are using hydroxychloroquine azithromycin. Perhaps antiviral that are discussed, here in, protease inhibitors like Nelfinavir, Indomethacin, Chloroquine, small interfering RNA (SiRNA), Ribavirin, Lopinavir demonstrated activity in reducing replication and viral protein expression in SARS 2003 may be better drugs for the treatment of this virus. However, it is better to leave it to doctors who are treating. This is based on earlier studies of 2003 and only a suggestion.

Indians broadly needed virologist would able to handle this type of virus as per the WHO protocol. In this present epidemiology, virus isolates from patients should be studied in vitro, in laboratory by virologist and suggest which drugs are the best. Simultaneously all the hospitals should maintain case studies to arrive which drug is best in future.

The most sensitive test to detect SARS was real time quantitative RT-PCR (polymerase chain reaction) Birds, pigs, cattle sheep, mice and rates were found to be negative as natural reservoir of SARS-CoV. Perhaps protease inhibitors nelfinavir (antiviral agent) Indomethacin and hydoxychloroquine were tested Invitro (laboratory tests) for cat SARS-CoV. There was no proven antiviral agent for any SARS but only supportive care. Invitro studies on SARS-CoV, small interfering RNA (SiRNA) demonstrated activity in reducing replication and viral protein expression of cell lines, Ribavirin, Lopinavir (antivirals)were also tested invitro.

Before confirming the presence of these types of SARS-viruses broad spectrum antibiotics, corticosteroids may be used, but when confirmed antivirals may be best option. Luckily the host of practical antiviral agents are available now for the treatment of HIV-AIDS. The primary mode of spread is person to person through micro droplets associated with cough and sneezing with an incubation period of 2-14 days. To prevent this virus to spread further "social distancing" that is the mantra in our minds and media now which was advocated back in 2007. Further the chores that we are supposed to follow now are isolation, quarantine, and usage of household bleach on surfaces to kill.

A collaborative effort by doctors, molecular biologists (to gene sequence to identify drug target sites), Virologists (in vivo) and chemists is the need of the hour. The efforts to test the chemicals drug candidates, screen the antivirals against virus isolates, molecular modelling and relentless drug discovery by chemists are expedient in the present context to tackle invasion of a future virus.

Covid-19 super disease is one of its kind that the modern world has seen. We need a community response from every Indian and protect our future. We have to leverage our limited resources and face the situation as people. The social distancing should not be an excuse to be away, we still need to help. We can win only with a community driven approach as it is beyond the resources of the government alone. Let's rise and fight the Coronavirus to the end.

(Dr K Nagaiah is Chief Scientist, CSIR-IICT, Hyderabad, Prof G Srimannarayana, is retired professor, Department of Chemistry,Osmania University, Hyderabad and Phaniraj G, is IT Professional, Boston, USA)