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Scientists develop mechanism to inactivate Covid by blocking entry to cells

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 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.

Maharashtra

Sadanand Data’s path to becoming DGP is paved, Data will succeed Rashmi Shukla in Maharashtra, will take charge from January 1

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NIA Chief Sadanand Date: The Appointments Committee of the Cabinet (ACC) of the Central Government has taken a significant administrative decision, approving the immediate repatriation of National Investigation Agency (NIA) Director General and senior IPS officer Sadanand Vasant Date to his parent cadre in Maharashtra. This order, issued on December 22nd, is considered highly significant from both an administrative and political perspective.

Sadanand Date is a 1990 batch IPS officer and is known as a strict, honest, and experienced officer at both the central and state levels. During his tenure as NIA chief, the agency’s role in several sensitive and national security-related cases was further strengthened. Under his leadership, the NIA’s efficiency and credibility have increased.

This decision comes at a time when elections for the Brihanmumbai Municipal Corporation (BMC) are scheduled for January. The BMC is one of the largest municipal corporations in the country, and maintaining law and order during its elections is a major challenge for the state police. Therefore, experienced leadership at both the central and state levels is considered crucial.

The term of the current Director General of Police (DGP) of Maharashtra, Rashmi Shukla, ends on December 31st. In this context, Sadanand Date’s name is being considered as a frontrunner for the next DGP of the state. According to administrative sources, Date’s appointment could ensure a fair and robust security arrangement during the elections.

Sadanand Date is known as the courageous officer who directly confronted terrorist Ajmal Kasab at the Cama and Albless Hospital during the 26/11 Mumbai terror attacks. He was seriously injured during the incident, but his courage and dedication to duty earned him national recognition.

If Sadanand Date is appointed as the new DGP of Maharashtra, it will be considered a major and positive step for the state’s law and order and security apparatus. Administrative circles believe that his appointment will boost the morale of the police force and help in conducting the upcoming elections peacefully.

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Maharashtra

Mumbai: Rickshaw driver beaten up in Vikhroli on suspicion of child theft, burqa-clad driver did this to collect fare, police claim

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Mumbai: Vikhroli Park Site, after the rumor of a child theft, chaos broke out and an auto rickshaw driver was attacked by a mob when he went to the street of Vikhroli Madina Masjid dressed in a burqa to collect his fare. During this, people suspected that the child had come to steal, after which the mob beat him up, but the police reached the spot and then took him into their custody. During interrogation, it was found that the child had not come wearing a burqa to steal but to collect the fare. He was dressed in a burqa so that no one would recognize him and he could easily collect his fare and go back, but unfortunately, the people caught him and the police took him out of the mob’s possession and safely took him to the police station. After that, the police confirmed that the child had not come to steal. Further investigation is underway in this matter. The police said that along with the investigation, it is also being found out whether he really came to collect the fare or not. He is a thief. Initial investigation has revealed that the child is not a thief. The police have confirmed that the rickshaw driver is not a thief.

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Maharashtra

Municipal Corporation in Mumbai is committed to conducting administration and election process in a fearless, free and transparent environment: Bhushan Gagrani

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Mumbai: Municipal Corporation Administration and Election System Mumbai Municipal Corporation is committed to conducting the election process for the general elections 2025-26 in a completely fearless, free, transparent and disciplined environment. In this regard, the Mumbai Municipal Corporation Administration has made all and extensive preparations and all necessary measures are being implemented effectively. The role of political parties is very important in the election process. In order to promote democratic values ​​and make the election process fair, transparent and credible, all political parties, their office bearers and workers should strictly follow the code of conduct framed by the State Election Commission and cooperate with the Municipal Corporation Administration. A positive and exemplary example should be set in the electoral process, this appeal was made by Municipal Commissioner and District Election Officer Bhushan Gagrani. A meeting was held with representatives of political parties at the Municipal Corporation headquarters today in connection with the Mumbai Municipal Corporation general elections 2025-26. On this occasion, Gagrani presented detailed information about various administrative, technical and legal aspects of the elections.

Additional Municipal Commissioner (City) Dr. Ashwini Joshi, Special Duty Officer (Election) Vijay Balmwar, Joint Commissioner (Tax Assessment and Collection) Vishwas Shankarwar, Assistant Commissioner (Taxation and Collection) Gajanan Belle, UP Election Officer Vijay Kumar Suryavanshi and other office bearers and representatives of various political parties were present in the meeting. Political parties were provided detailed information about the offices of 23 Election Decision Officers and their scope of work for the smooth conduct of the elections. Along with this, guidance was also given on the process of filing nomination papers, scrutiny of applications, registration of objections and how to contact these offices for day-to-day work in the election process. Municipal Commissioner Shri said that all necessary arrangements have been completed at the level of the Election Decision Officer so that the candidates do not face any technical problems.

Additional Municipal Commissioner (City) Dr. Ashwani Joshi said that all guidelines have been given so that the candidates do not make any mistakes while filing nomination papers (candidate applications) for the elections. The concerned persons should submit all the information in the prescribed format. Candidates should take special care that no application is rejected due to technical difficulties. It is mandatory for the candidates to fill all the information correctly and clearly in the affidavit submitted with their application. He said that if any column is left blank in the affidavit or if incorrect information is found, the nomination of the candidate, along with all other matters, can be cancelled.

Joint Commissioner (Tax Assessment and Collection) Vishwas Shankarwar said that the main objective of the administration is to increase the voting percentage to strengthen democracy. For this, political parties should create awareness among the voters. Public awareness is being created among the voters under the ‘SVEEP’ program by the Municipal Corporation. Also, it is mandatory to follow the guidelines of the esteemed State Election Commission regarding election expenses. Candidates should keep a record of every expense incurred during the election campaign and submit the account of election expenses within the stipulated time. Various doubts raised by the representatives of political parties on various issues were cleared including caste verification certificate, toilet usage certificate, Appendix 1 and Appendix 2, appointment of representatives of election candidates.

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