SB43154 drug used in cancer research shows promise against COVID-19 in preclinical studies: Scientists
Remarkably, even after more than 50 consecutive generations exposed to the drug, the virus was unable to develop resistance. Scientists from the Indian Council of Medical Research (ICMR) and Indian Council of Agricultural Research (ICAR) have jointly found that the drug — SB431542, an ALK5 inhibitor — is highly effective against the coronavirus.
New Delhi, Jul 28 (PTI) After a long battle and research, Indian scientists have found out that a drug used in cancer studies has the potential to provide substantial protection against the coronavirus infection in preclinical studies.
The study was first released as a preprint on bioRxiv and has since been accepted for publication in the Journal of Virology. If future human trials confirm its effectiveness, the drug could become a groundbreaking tool in the fight against COVID-19.
Since December 2019, when the coronavirus emerged from China's Wuhan, it has spread to nearly every country in the world. Since 2020, more than 30 anti-Covid vaccines have received the World Health Organization's (WHO) approval for global use.
'However, health experts believe vaccines alone are not enough. The virus continues to mutate, and many existing treatments like Remdesivir and monoclonal antibodies will quickly lose effectiveness,' Kumar said.
In this context, Indian scientists have been screening small molecule inhibitors that mainly target cellular kinases and phosphatases. One such compound, SB431542 — originally developed to block TGF-β (Transforming Growth Factor-beta) signalling and commonly used in preclinical cancer, inflammation and fibrosis research — has now been found by Indian researchers to also inhibit the coronavirus effectively.
Kumar explained that SB431542 fights the virus in three fronts. It first blocks the virus from entering human cells by targeting the TGF-β/Smad pathway. Secondly, it disrupts the ability of the virus to assemble inside cells by interfering with ORF3a-related lysosomal dysfunction. Finally, it prevents the virus from killing the infected cell (a process called apoptosis), which helps stop the virus from escaping and spreading to other cells. This three-pronged approach has not been observed in any existing antiviral drug.
Interestingly, the drug acted through both direct and indirect mechanisms — it directly targets the viral ORF3a protein and indirectly hinders the virus by blocking the host cell's TGF-β signaling pathway.
SB431542 was also tested against the chicken coronavirus (Infectious Bronchitis Virus or IBV) in specific pathogen-free chicken embryos. Embryos treated with the drug developed normally and showed no mortality, while those in the untreated control group failed to develop properly and did not survive.
Kumar emphasised that even after exposing the virus to the drug over 50 successive generations (passage), it failed to develop resistance. This suggests that the chances of the virus evolving a drug-resistant variant against this compound are extremely low. This is a major advancement over existing antivirals like Remdesivir, against which the virus builds resistance quickly. PTI PLB RC
This report is auto-generated from PTI news service. ThePrint holds no responsibility for its content.
Hashtags
Try Our AI Features
Explore what Daily8 AI can do for you:
Comments
No comments yet...
Related Articles
Hindustan Times
5 minutes ago
- Hindustan Times
ICMR's anti-malaria vaccine still 6-7 years away
The Indian Council of Medical Research (ICMR) has invited an expression of interest for technology transfer to commercialise its anti-malaria vaccine candidate that it is developing in partnership with the department of biotechnology, even though the vaccine is likely to take at least six to seven years to be ready for use, according to people familiar with the matter. Malaria continues to pose serious challenges to public health and economies, particularly in the tropical and subtropical regions around the world. (Unsplash) According to the projected timeline, accessed by HT, the 'Good Manufacturing Practice (GMP) production and toxicology studies' will take approximately two years; 'phase 1 clinical trial, including regulatory approval', will take another two years; 'Phase 2b and Phase 3 clinical trials' will take approximately two and a half years; and post-trial regulatory clearance and licensing for marketing would take approximately six months. (Each stage includes a buffer period of ± six months.) The recombinant chimeric multi-stage malaria vaccine (AdFalciVax) is being indigenously developed against plasmodium falciparum— the parasite that predominantly causes severe and fatal malaria, according to ICMR. 'In early stages, the vaccine candidate looks useful in preventing plasmodium falciparum infection in humans and minimising its community transmission,' it added. Malaria continues to pose serious challenges to public health and economies, particularly in the tropical and subtropical regions around the world. According to data shared by the government, globally in 2023, there were almost 263 million estimated malaria cases in 83 malaria-endemic countries, an increase of 11 million cases compared with 2022. India accounted for half of all estimated malaria cases in the South-East Asia region in 2023. ICMR has invited applications from organisations, companies, and manufacturers from across the country. 'ICMR-Regional Medical Research Centre, Bhubaneswar (ICMR-RMRCBB)— one of the constituent institutes of ICMR has led development of a technology entitled 'A recombinant chimeric multi-stage malaria vaccine (AdFalciVax) against Plasmodium falciparum'… and ICMR-RMRCBB has technical know-how of process to produce this technology. The pre-clinical validation of this technology has been conducted in collaboration with ICMR-National Institute of Malaria Research (ICMR-NIMR), another constituent institutes of ICMR, and National Institute of Immunology (NII), New Delhi, an autonomous research institute of the Department of Biotechnology, Government of India,' the ICMR invite said. AdFalciVax is the first indigenous recombinant chimeric malaria vaccine specifically designed to target two critical stages of plasmodium falciparum. Country's biomedical research regulator, however, emphasised that the vaccine candidate is in its early research and development phases and is not yet available for any clinical use or commercialisation. The vaccine has shown excellent efficacy in the preclinical stage of development, ICMR said in a statement. 'Preclinical data suggest that AdFalciVax may have advantages over existing single-stage vaccines (such as RTS,S/AS01 and R21/Matrix-M), including: Broader protection by targeting two vulnerable parasite stages; lower risk of immune evasion and potential for better long-term immunity; extended thermal stability with functionality maintained for over nine months at room temperature; and cost-effective formulation using pharmaceutically acceptable carriers,' the statement added. ICMR further said that it intends to licence the technology for AdFalciVax to eligible organisations and manufacturers for further development, manufacture, and commercialisation under non-exclusive agreements. This approach aims to enable wider outreach and maximize public health benefits, and all collaborations will adhere to ICMR's intellectual property policy. ICMR would provide technical support through its team of experienced scientists in study planning, product development, development of study protocol, results or data analysis, outcome assessment, safety and efficacy assessment, product improvement, etc. 'Subsequent to the execution of the agreement such companies/manufacturers shall be responsible to pay the Royalty @ 2% on Net sales, as applicable, according to the ICMR Guidelines for Technology Development Collaboration...,' the statement said. It added that the introduction and rollout of malaria vaccines, such as RTS,S and R21/Matrix-M, have shown promise in reducing disease incidence, particularly among young children in high-burden areas. While significant progress has been made in combating malaria, the global burden remains substantial. In order to address the goal of malaria elimination, an improved vaccine with better efficacy needs to induce protection against infection in human hosts as well as block or reduce transmission to the mosquito vector. 'In this proposed technology, we developed a process for the production of P. falciparum recombinant chimeric malaria antigen (AdFalciVax) … and have tested it for improved immunogenicity with different adjuvant formulations… It has been hypothesized that a combination of Pre-erythrocytic/Anti-Infection Vaccines (AIV) with Transmission-blocking Vaccines (TBV) will reduce the force of infection and be more efficacious than an AIV, like RTS,S or R21/Matrix-M alone,' the statement added.
Indian Express
5 minutes ago
- Indian Express
Intervention by Indian team helped fix key issue before Axiom-4 launch: ISRO chief
Weeks before it finally took off, the Axiom-4 mission, which carried Group Captain Shubhanshu Shukla and three other astronauts to the International Space Station (ISS), was nearly cleared for launch despite a perceived minor oxygen leak — until an ISRO team insisted on further checks that revealed a potentially dangerous crack in the rocket, ISRO Chairperson Dr V Narayanan told The Indian Express. The Axiom-4 mission took off for space from NASA's Kennedy Space Center in Florida on June 25 after a series of delays since the initial launch date of May 29. The first launch was deferred to June 8 due to an electrical issue in the SpaceX Dragon spacecraft — the module where the crew was seated. But on June 8, when the engines were test-fired on ground, an oxygen leak was observed in addition to an anomaly in one of the actuators, used in controlling the direction of the rocket's thrust. Dr Narayanan told The Indian Express that the oxygen leak was deemed minor and unlikely to affect the launch, but the Indian team — 18 scientists including the ISRO chairman and the director of the Human Space Flight Centre — embedded with the Axiom-4 and NASA teams felt something was amiss and pushed for further checks. 'Initially the team thought that there was a minor leak and the mission could proceed as planned. But, the Indian team insisted that proper checks be carried out even if it meant delaying the mission. And it was good that the tests were carried out because a crack was detected, allowing for repair. It was resolved before the mission took off,' Dr Narayanan said. The crack was in the oxidiser line, which carries liquid oxygen to power the rocket — a serious safety risk, especially for a crewed mission. The crack and other issues were fixed, but on June 12 NASA announced it was working with Russian space agency Roscosmos to evaluate a leak in the Zvezda module, the Russian-built service module of the ISS that houses key life-support and docking systems. This further delayed the mission until the final launch two weeks. During the mission, the Indian team was present at both Kennedy Space Center in Cape Canaveral where launch operations took place and at mission control in Houston, Texas, where real-time flight operations are managed — from crew health monitoring and communications to emergency response. Dr Narayanan described the mission as a significant step forward for ISRO's human spaceflight programme, with astronaut training emerging as its single most valuable takeaway. He said Indian scientists got hands-on exposure to how crewed missions are run — from making real-time decisions and interpreting telemetry data to monitoring astronaut health and responding to in-flight contingencies. 'It was like a classroom where we learnt a lot by working with the other teams there,' he said. 'The experience was important for understanding how human space missions are run at an operational level… The training of the astronaut — especially with someone as experienced as the commander — was a big learning experience for the Indian team.' Axiom-4 commander Peggy Whitson, a veteran astronaut, holds the record for the most number of days spent in space by an American or a woman — 695 days across multiple missions. India plans to build a sustained human spaceflight programme, with a space station targeted by 2035 and a human Moon mission by 2040. This will require setting up a permanent astronaut corps and regularly training new astronauts, like NASA and Roscosmos do. In addition to the training, Dr Narayanan said Shukla's experience of living in microgravity, staying in an isolated environment and returning to Earth would be invaluable for India's own programme. ISRO has asked Shukla to document his entire experience in detail. 'This,' Dr Narayanan said, 'would become teaching material for his fellow astronauts as well as the other astronauts to come.' Shukla, who returned to Earth with a splashdown on July 15, is currently undergoing reconditioning in the United States. He is expected to remain in quarantine until the first week of August, after which he will participate in a debriefing with NASA and return home by mid-August.
The Hindu
an hour ago
- The Hindu
From The Hindu, August 4, 1975: NASA invites India to join space shuttle experiment
Ahmedabad, Aug. 3: The National Aeronautics and Space Administration (NASA) has invited India to propose an experiment that could be placed in the space shuttle, scheduled to become operative in 1980. An Indian scientist can accompany the experiment in the space shuttle also, said Mr. Arnold Frutkin, Assistant Administrator for International Affairs, NASA, in an interview to a local daily here. Mr. Frutkin, who played a leading role in India's Satellite Instructional Television Experiment was here to watch its inauguration on August 1. He said the European countries participating in the research project aboard the shuttle might send a scientist. The space shuttle was the next major project of NASA after the Apollo programme had ended, he added. 'It is less costly ($12 billions) but is expected to be a major milestone in space travel as it will try the concept of reusable booster,' he said. Mr. Frutkin said the cargo bay of the shuttle would be 60 feet long and 15 feet wide. The space shuttle, well past the design stage, would also carry an entire laboratory and change the way 'you do business in space. It will make space travel cheaper,' he added. Mr. Frutkin said the costs were bound to go down if the same booster could be used over and over again.
