General
Scientists develop mechanism to inactivate Covid by blocking entry to cells
Scientists have developed a design of a new class of synthetic peptides that can not only block the entry of SARS-CoV-2 virus entry into cells but also clump the virions (virus particles) together, reducing their ability to infect.
Scientists at the Indian Institute of Science (IISc), in collaboration with researchers from the CSIR-Institute of Microbial Technology, have made use of this approach to design peptides that can bind to and block the spike protein on the surface of SARS-CoV-2 virus, said the Ministry of Science and Technology on Wednesday.
This binding was further characterised extensively by cryo-electron microscopy (cryo-EM) and other biophysical methods. This novel approach provides an alternative mechanism to render viruses like SARS-CoV-2 inactive, promising a new class of peptides as antivirals.
The research was supported under the Covid-19 IRPHA call of SERB Science and Engineering Research Board (SERB), a statutory body of Department of Science and Technology (DST).
The designed peptides are helical, hairpin-shaped, each capable of pairing up with another of its kind, forming what is known as a dimer. Each dimeric ‘bundle’ presents two ‘faces’ to interact with two target molecules.
In the study published in Nature Chemical Biology, the researchers hypothesised that the two faces would bind to two separate target proteins locking all four in a complex and blocking the targets’ action. The team decided to test their hypothesis by using a peptide called SIH-5 to target the interaction between the Spike (S) protein of SARS-CoV-2 and ACE2 protein, the SARS-CoV-2 receptor in human cells.
The S protein is a trimer – a complex of three identical polypeptides. Each polypeptide contains a Receptor Binding Domain (RBD) that binds to the ACE2 receptor on the host cell surface. This interaction facilitates viral entry into the cell.
The SIH-5 peptide was designed to block the binding of the RBD to human ACE2. When a SIH-5 dimer encountered an S protein, one of its faces bound tightly to one of the three RBDs on the S protein trimer, and the other face bound to an RBD from a different S protein.
This ‘cross-linking’ allowed the SIH-5 to block both S proteins at the same time. Under cryo-EM, the S proteins targeted by SIH-5 appeared to be attached head-to-head, and the spike proteins were being forced to form dimers.
Subsequently, the researchers showed that SIH-5 inactivated the viruses efficiently by cross-linking the spike proteins from different virus particles.
The team consisting of B Khatri, I Pramanick, SK Malladi, RS Rajmani, P Ghosh, N Sengupta, R Varadarajan, S Dutta and J Chatterjee from Indian Institute of Science (IISc), R Rahisuddin, S Kumar, N Kumar, S Kumaran and RP Ringe from CSIR-Institute of Microbial Technology, tested the peptide for toxicity in mammalian cells in the lab and found it to be safe.
When hamsters were dosed with the peptide and subsequently exposed to a high dose of SARS-CoV-2, they showed decreased viral load as well as much less cell damage in the lungs compared to hamsters exposed only to the virus, demonstrating the promise of this class of peptides as antivirals.
The researchers believe that with minor modifications and peptide engineering, this lab-made miniprotein could inhibit other protein-protein interactions as well.
SOURCE: FREE PRESS JUORNAL
Mumbai : Mumbai citizens have been hit by inflation ahead of the BMC elections. The fare hike for BEST buses has been approved. An additional fare of twice the fare will be implemented from today, which will now mean that BEST passengers will have to pay an additional fare, which will affect the pockets of the passengers. The BEST administration has decided to implement the new fare from May 9. The fare has been increased for distances of 5, 10, and 20 kilometers.
The fare for a distance of 5 kilometers has been doubled. The fare for a distance of 5 kilometers has been increased from Rs 6 to Rs 12. No concession has been given in the fare for a 12-year-old child. The daily pass was previously Rs 60, but now the new fare has been increased to Rs 75. The monthly pass is from Rs 900 to Rs 1,800. The facility of Chalo Bus Pass has been provided for children of the Municipal Corporation. The increase in bus fares and tickets in Mumbai has put a burden on the pockets of the citizens. Shared taxis and auto rickshaws are also operated in Mumbai city and its suburbs, but due to the fare, many passengers are unable to pay for these shared means of transport and travel by buses.
Mumbai: The verdict in the September 29, 2008 bomb blast in Malegaon will be pronounced on July 31. BJP leader and former MP Sadhvi Pragya Singh Thakur, Lt. Col. Srikant Prasad Purohit, former Major Ramesh Upadhyay, Sudhakar Dwivedi, Sudhakar Chaturvedi, Swami Dayanand Pandey, Ajay Rahirkar, and Sameer Kulkarni are accused of being involved in illegal activities. A bomb was planted in Sadhvi Pragya Singh Thakur’s scooter, after which the Maharashtra Anti-Terrorism Squad (ATS) arrested 13 accused in the case and charged 7 accused. The hearing of the Malegaon bomb blast will be completed in April. The verdict was expected to be pronounced today, but the court gave the reason that more than one lakh pages are under study and therefore the matter has been adjourned till July 31.
A bomb blast in a scooter at Bhakko Chowk killed 7 people and injured 100. In this case, ATS Chief Hemant Karkare investigated and MCOCA was also applied to the accused, but this investigation was later handed over to the NIA in 2011. The NIA has sought death penalty for the accused in this case. Statements of 223 witnesses were recorded in this case and 23 witnesses defected in the court, including 8 witnesses from the army and defense department. The court has ordered all the accused to be present on July 31 and if anyone is absent, action will be taken against him. The court will pronounce its verdict in this case only on July 31 because the hearing of the case has been completed and the court has also reserved its verdict.
Maharashtra
Digital Rakshak secures money of five complainants who were scammed in the name of Digital Arrest
Mumbai: Five complainants who were scammed on social media in the name of digital arrest through the Mumbai Police’s Digital Rakshak (Digital Protector) have been protected by the Digital Rakshak. In Mumbai, CBI, ED and police officers send notices on social media and WhatsApp in the name of Digital Arrest, demanding huge money for video calling in the name of investigation and saving them from the case in the name of investigation. Accordingly, Mumbai Police has developed the Digital Rakshak app. The complaint of five victim complainants was processed on this helpline. In Mumbai’s Chembur area, a video call was made to an elderly person on social media calling him Digital Arrest and it was said that he had huge money in his bank account and his documents, Aadhaar card and PAN card were used in illegal activities.
The caller on the call told the elderly person that he was a CBI officer and demanded money without disconnecting the video call. During this, the victim When the daughter entered the house, she found her father scared and then she asked her father why he was scared. On this, the father told her that it was a call from a CBI officer and that he had transferred money in this matter. After that, the victim contacted the Mumbai Police’s Digital Rakshak helpline and then informed the police about this notice. After that, it was confirmed that this notice was prepared by the CBI and ED by creating a fake notice and sending it on WhatsApp. The police have resolved five cases of digital arrest and have appealed to the citizens that no security agency does digital arrest and neither is investigation done on WhatsApp, so be careful of such elements.
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