Scientists have discovered a way to stop the COVID-19 virus from replicating in infected human cells, marking major progress towards a definitive treatment for the deadly illness and accentuating the potential of genetic engineering to cure viral diseases.
The study explores the use of CRISPR, a genome editing tool, and builds on research that started at Australia’s Peter MacCallum Cancer Center in 2019, when Dr. Mohamed Fareh and Prof. Joe Trapani showed that CRISPR could be used to eliminate abnormal RNAs that drive children’s cancers.
At the beginning of the pandemic, and in collaboration with Director Prof. Sharon Lewin and Dr. Wei Zhao from the Doherty Institute, the scientists reprogrammed the same CRISPR tool to suppress replication of the RNA virus SARS-CoV-2 — and importantly, its “variants of concern” — in a test tube model. SARS-CoV-2, which is short for Severe Acute Respiratory Syndrome Coronavirus 2, is the virus that causes COVID-19.
“The CRISPR approach is for a treatment,” lead scientist Lewin told the Alliance for Science. “There are currently no good antiviral drugs available for COVID-19. CRISPR can efficiently destroy the virus.”
At the core of the research is an enzyme (CRISPR-Cas13b) that binds to target RNAs and degrades the part of the virus’ genome needed to replicate inside cells.
The scientists applaud the specificity, efficiency and rapid deployment properties of reprogrammed Cas13b, which provides a blueprint for antiviral drug development to suppress and prevent a wide range of SARS-CoV-2 mutants. The same properties can be readily deployed to fight off other pathogenic viruses.
“The flexibility of CRISPR-Cas13, which only needs the viral sequence, means we can look to rapidly design antivirals for COVID-19 and any new emerging viruses in less than a week,” Fareh said. There were signs that this approach could also be applied to a host of existing viruses, signalling a game-changer for how they are currently treated, he added.
“Unlike conventional anti-viral drugs, the power of this tool lies in its design-flexibility and adaptability, which make it a suitable drug against a multitude of pathogenic viruses including influenza, Ebola, and possibly HIV,” Fareh said.
Lewin also remarked on CRISPR’s potential in developing cures for viral diseases,
“This technique is highly relevant to new RNA viruses,” she said. “When we discover a new virus, the first thing we can do is get its genetic code. This is relatively easy to do. For COVID-19, we had the genetic code on Jan. 10. For CRISPR, we just need the genetic code to make a product. We think this approach is ideal for tackling new viruses in future pandemics.”
The researchers note that mutation-driven viral evolution, such as the COVID variants now circulating, can generate drug resistance, immune escape and increased efficiency of transmission and pathogenicity, all of which are detrimental to the patient. Fareh explained that the constant emergence of new variants is threatening the efficacy of various vaccines as the virus evolves and escapes the host immune system.
“Recent data suggest that the community would likely need booster vaccines to update our immunity against new variants, which will bring additional manufacturing and world-wide distribution logistic challenges,” Fareh told the Alliance. “There are also immuno-compromised individuals in the communities, such as the high HIV-positive population in sub-Saharan African countries, who can’t benefit from vaccines and remain vulnerable to this virus.”
“The long term goal is that if someone has a positive test for COVID-19, they immediately take CRISPR-Cas13 to stop the virus progressing to the lungs or triggering disease. This would also reduce the amount of virus in the nose and reduce the chance of transmission,” Lewin stated, adding that the treatment would take the same approach used in HIV management.
“This is exactly how HIV drugs work,” she continued. “Antiviral drugs for HIV reduce the amount of HIV in the blood allowing for an HIV-infected person to be healthy. At the same time the drugs reduce transmission. In HIV, we term this treatment as prevention.”
Lewin said that while the pandemic response is focused on rolling out protective vaccines, there remains an urgent need for treatments specific to COVID-19 patients.
The team is currently working on animal models and anticipates that the treatment might be available for clinical use in two years, at the minimum. Such an approach could be welcome news for vulnerable communities that have borne the brunt of inadequate access to vaccination against the pandemic, such as Africa.
Fareh told the Alliance that inequity in vaccines access between rich and poor nations has left African countries largely unvaccinated and vulnerable to the virus from both health and socio-economical perspectives.
“What is exciting about this new drug we developed is its ability to suppress many — if not all — variants due to its resilience to viral evolution,” he said. “This resilience may provide the community, including poorer countries, with a single drug that is effective against all SARS-CoV-2 strains, which is an attractive option from a health and logistic point-of-view.”
Image: Coronavirus COVID-19 infection 3D medical illustration. Shutterstock/Corona Borealis Studio