‘Mortality rate is greater in pandemic caused by a Genetically Engineered Virus’

Coronavirus continues to wreak havoc across the world. The vaccine for this virus is nowhere in sight and we are still not sure if the genetic make up of Novel Coronavirus was altered inside a Wuhan laboratory in China. Dr Rajesh Mehrotra, scientist at BITS Pilani and an expert in the field of Cis Regulatory Elements in DNA, said in this e-mail interview with Vivek Sinha that human cells cannot distinguish between a man made virus and a natural strain of virus. He explained that genetic alterations of a virus cannot be done in the backyard laboratory by a rogue scientist.

Vivek Sinha: Coronavirus epidemic has taken the world by storm. Several conspiracy theories are floating around the world about origins of this virus from China. What is the buzz within scientific community about the origins of Novel Coronavirus?
Dr. Rajesh Mehrotra: Coronavirus originates in animals like bats and pangolin and are not transmissible to humans until and unless a (virus) strain is mutated that can pass from animals to humans and then from human to humans. Also, an article published in Nature Medicine on 18th March 2020 rubbished the concern that it was man made because at a molecular level its genetic data does not came from any previously used virus backbones.

Vivek Sinha: What does it take to genetically engineer a naturally occurring virus and turn it into a lethal strain? How is the human immune system foxed by these genetically engineered virus strains and why is it unable to respond as quickly as in the case of a natural strain of the virus?
Dr Rajesh Mehrotra: In any good laboratory with proper Biosafety levels (BSL-3 or above) one can engineer a naturally occurring virus. Genetic modification involves the direct insertion, deletion, artificial synthesis (using phosphoramidite chemistry), or change in nucleotide sequences in viral genomes using biotechnological methods which can turn a strain into lethal strain. Immune response to virus is via three modes (i) Cytotoxic Cell (ii) Interferons and (iii) Antibodies. Viruses are highly adaptable and have developed ways to avoid detection by cells. Some viruses stop Major Histocompatibility Complex molecules from getting to the cell surface to display viral peptides. If this happens, the cell doesn’t know that there’s a virus inside the infected cell.

Vivek Sinha: Does it require a sophisticated laboratory to manipulate the genome of a virus or can this be done by a rogue scientist in the backyard laboratory of his home? 
Dr Rajesh Mehrotra: It is recommended to use BSL-3 or above that is Biosafety Level–4 (BSL-4). This is the maximum containment level and is designed to be used for manipulating emerging viruses with the highest level of risk. And, it cannot be done in the backyard laboratory.

Vivek Sinha: Can a genetically engineered virus (man-made virus) be distinguished from a naturally occurring virus though any tests? If yes, what are these tests and if No, why is it difficult to differentiate between a man-made virus from a naturally occurring virus? 
Dr Rajesh Mehrotra: To the best of my understanding we cannot differentiate between a man made virus and a naturally occurring virus. Viruses in general have a very simple structure. They have capsid or protein and DNA or RNA as a genetic material. Once the strain is genetically modified using phosphoramidite chemistry it cannot be distinguished whether a strain is man-made or natural.

Vivek Sinha: Is mortality rate greater in a pandemic caused due to genetically engineered virus, vis-a-vis a natural virus strain? Why is it so?  
Dr Rajesh Mehrotra: Yes, mortality rate is greater in a pandemic caused due to genetically engineered virus because new viral proteins are sufficiently different from preexisting viral proteins, and due to this there may be a limited immune recognition by humans. As a result, the majority, if not all, of the human population may be susceptible to the new viral form. In addition, reassortment may also result in a very virulent new strain.

Vivek Sinha: Do you think Coronavirus will be able to survive in Indian summer? And is there a possibility of its recurrence during the upcoming monsoon months or during the onset of next winter season?
Dr Rajesh Mehrotra: Drawing corollary from Australia, which just experienced its peak summer season but still reported 400 confirmed cases, I think the virus will be able to survive Indian summer. However, a decline in the contagiousness of COVID-19 may be observed in the coming summer days, but the transmission of the virus will nevertheless remain very much possible.

Vivek Sinha: Coronavirus has spread and/or it’s spreading like wildfire across the Eastern and Western sides of India. How long can India stay safe before Covid-19 becomes an epidemic in India?
Dr Rajesh Mehrotra: Indian government is making all efforts that we don’t reach to the stage of community transfer and restrict it in at Stage-2. Next seven days is going to be very crucial for us. If we can keep the count low, then perhaps we will reduce the chance to enter Stage-3 and India stays safe or else we will succumb.

Vivek Sinha: It’s still unknown if India has silently entered the Stage -3 of Coronavirus outbreak where the virus spreads across communities. How are things expected to pan out in India? What else can India and other SAARC nations do to control this pandemic?
Dr Rajesh Mehrotra: Number of confirmed cases for COVID-19 are indicative of the fact that we may be slowly moving towards the Stage-3. Across the globe, social distancing is one option available with governments. Indian government has been proactive. In Indian context social distancing is the most important measure being advocated by the government and the Janta curfew has been asked by our Prime Minister Mr. Narendra Modi to be imposed on Sunday, 22^nd March to break the chain of transmission. The curfew time requested is 14 hours and the virus can only survive for 12 hours outside a living host.

However, there are many other parameters to be looked into, which includes age composition of the population, high risk population, latency period (the amount of time from initial infection to illness), infection period (the time infected individual remains contagious to other people), population density, personal behavior, climate and environment. SAARC nations will have many common factors but some unique factors (such as the age of those being infected) need to be identified by respective governments and they must take strong measures to curb the crisis.

Vivek Sinha: If Covid-19 is a biological weapons programme gone out of control, will the scientific community, doctors and healthcare professionals be able to control the spread of this Novel Coronavirus?
Dr Rajesh Mehrotra: One of the hypothesis in air is about it being a biological weapon and we cannot rule it out completely, though scientists from UK confirmed that at a molecular level COVID-19 genetic data does not come from any previously used virus backbones. Efforts to develop vaccines are already in place and I believe we will have some lead from USA by December-end.