Type of vaccine against monkeypox (GS Paper 3, Science and Tech)
Why in news?
- With the World Health Organization (WHO) declaring monkeypox as a Public Health Emergency of International Concern (PHEIC) and cases rising globally to around 19,179 in 78 countries, governments around the world are initiating steps towards developing or even sourcing a vaccine against monkeypox.
Are there vaccines for monkeypox?
- The monkeypox virus belongs to a family of viruses called orthopoxviruses, which is different from that of the coronaviruses. According to the WHO, it is a viral zoonosis, a virus transmitted to humans from animals with symptoms similar, but less severe to smallpox.
- It is also an enveloped double-stranded DNA virus, unlike the RNA virus, that makes it far more stable and less prone to rapid mutations.
- There are two distinct genetic clades of the monkeypox virus: the central African (Congo Basin) clade and the West African clade. The Congo Basin clade has historically caused more severe disease and was thought to be more transmissible.
- There is yet no dedicated monkeypox vaccine, but vaccinations against smallpox was found to be 85% effective in preventing smallpox, a disease eradicated in 1980.
JUNNEOS Vaccine:
- In 2019, the United States Food and Drugs Administration (FDA), approved the JYNNEOS vaccine for the prevention of smallpox, monkeypox and other diseases caused by orthopoxviruses, including vaccinia virus, in adults 18 years of age and older and categorised as having a “high risk of infection.”
- These include contacts of those who have been confirmed to have contracted a monkeypox infection, sexual partners (with contact within previous two weeks) of those confirmed with an infection and those whose immune systems are compromised.
How does JYNNEOS work?
- JYNNEOS, developed by Danish biotechnology company, Bavarian Nordic, contains a live vaccinia virus that does not replicate efficiently in human cells.
- The vaccinia virus is the smallpox virus but made incapable of replicating within the body. It is administered as two injections 28 days apart. The immune response takes 14 days after the second dose.
- The evidence for JYNNEOS’ effectiveness against monkeypox rests on 22 clinical trials that tested the vaccine’s safety on 7,859 people, aged 18-80, who were administered at least one dose of the vaccine. Like in other vaccines, a percentage of individuals reported pain, fever, rashes, nausea and chills following the doses.
- The vaccine’s effectiveness was inferred only indirectly by comparing the immunogenicity of JYNNEOS to a licensed smallpox vaccine (ACAM2000) based on a laboratory test called the Plaque Reduction Neutralisation Test (PRNT). This test evaluates what quantity of the vaccine was needed to kill the virus made to replicate in a petri-dish.
- Because of structural similarities to the smallpox virus, the effectiveness of the JYNNEOS is estimated based on comparison to another licensed, smallpox vaccine called ACAM2000.
What about India?
- The Indian Council of Medical Research and the National Institute of Virology Pune have isolated the virus strain from samples of people confirmed with the infection in India; there have been four confirmed cases of monkeypox in India so far.
- The genomic sequence of the Indian strain has a 99.85% match with the West African strain circulating globally. The ICMR has invited tenders from local companies to develop a vaccine.
- The Serum Institute of India said it was in talks with international partners regarding a potential vaccine but that it would take time. However, despite its infectiousness, monkeypox is largely a contained disease that doesn’t attack vital organs and is as yet, not airborne.
COVID-19’s origin
(GS Paper 3, Science and Tech)
Why in news?
- A recent paper contained a post- facto analysis that the emergence of SARS-CoV-2 occurred via the live wildlife trade in China and established the Huanan market in Wuhan as the epicentre of the pandemic.
- While this is unlikely to seal forever the controversial debate over two years, including counter theories of a lab leak that led to the virus causing havoc in the world, it brings the issue to the first-of-its-kind empirical evidence-based averment and declaration on the origin of the SARS-CoV-2 virus.
- It is important to produce and examine the evidence on this account, as understanding how the virus emerged is perceived as essential to preventing further outbreaks of zoonotic diseases.
What does the Science paper show?
- During the early stages of the COVID-19 pandemic, the dominant hypothesis was that animals sold at the Huanan market were the likely source of the unexplained pneumonia cases. This led to the closure of the Huanan market on January 1, 2020.
- The original theory that the earliest known COVID-19 cases from December 2019, were geographically centered on this market. It shows that live SARS-CoV-2 susceptible mammals were sold at the market in late 2019. The analysis indicated a clear and present link between the market and the emergence and spread of the deadly virus.
- Of the initial 41 people hospitalised with unknown pneumonia by January 2, 2020, 66% had direct exposure to the Huanan Wholesale Seafood Market. These first cases were confirmed to be infected with a novel coronavirus, subsequently named SARS-CoV-2, and were suffering from a disease later called COVID-19.
- These early reports were free from ascertainment bias as they were based on signs and symptoms before the Huanan market was identified as a shared risk factor.
- A systematic review of all cases notified to China’s National Notifiable Disease Reporting System by hospitals in Wuhan showed that 55 of 168 of the earliest known COVID-19 cases were associated with this market. However, this alone could not indicate that the pandemic started there.
What methodology did the authors use?
- While early COVID-19 cases occurred across Wuhan, the majority clustered in central Wuhan near the west bank of the Yangtze River, with a high density of cases near to, and surrounding, the Huanan market.
- In a kernel density estimate (KDE) using the 120 cases with no known linkage to the market, the market remains within the highest density 1% contour.
- Using a COVID-19 assistance app on Sina Weibo, the researchers discovered that unlike early COVID-19 cases, by January and February, many of the sick who sought help resided in highly populated areas of the city, and particularly in areas with a high density of older people.
- The authors considered three categories of cases, and they were all significantly closer to the Huanan market than expected — all cases, cases linked directly to the Huanan market and cases with no evidence of a direct link to the Huanan market.
- They also performed a spatial relative risk analysis to compare December 2019 COVID-19 cases with January-February 2020 cases, reported via Weibo. The Huanan market is located within a well-defined area with high case density. No other regions in Wuhan showed a comparable case density.
- A report stated that only lineage B (of the two identified, A and B) sequences had been sampled at the Huanan market. Eleven lineage B cases from December 2019 resided closer than expected to the Huanan market. The authors went on to show that both identified lineage A cases had a geographical connection to the market, supporting the assumption that the virus was spreading outwards of the Huanan market.
- They reported that multiple plausible intermediate wildlife hosts of SARS-CoV-2 progenitor viruses, including red foxes, hog badgers and common raccoon dogs, were sold live at the Huanan market up until at least November of 2019.
What were the limitations to the study?
- Clearly, events upstream of the market, as well as exact circumstances at the market, remain obscure, highlighting the need for further studies to understand and lower the risk of future pandemics.
- In a post-facto analysis, not having access to the precise latitude and longitude coordinates of all these cases, lacking direct evidence of an intermediate animal infected with a SARS-CoV progenitor virus, and the lack of a line list of early COVID-19 cases are acknowledged as drawbacks.
Way Forward:
- The authors have called for maximum effort to elucidate the upstream events that might have brought SARS-CoV-2 into the Huanan market, culminating in the COVID-19 pandemic.
- To reduce the risk of future pandemics we must understand, and then limit, the routes and opportunities for virus spillover.
One step closer to precision cancer therapies
(GS Paper 3, Science and Tech)
Why in news?
- A recent research found a combination of molecules that can be used for developing novel anti-cancer therapeutics
- The work over the last decade has helped identify a new target for killing cancer cells, opening the door for potential new therapy.
The target pathway is utilised by cancer cells to repair DNA double-stranded break repair. 
Topoisomerase 1-targeted chemotherapy:
- Topoisomerase 1-targeted chemotherapy is one of the mainstays of treating cancer cells. Currently-used anti-cancer drugs (Camptothecin, Topotecan and Irinotecan) target a molecule (the enzyme Topoisomerase 1 or Top1) involved in DNA replication. While DNA replication is essential to cell division, runaway replication characterises cancer.
- However, they found that cancer cells sometimes develop resistance to Topoisomerase 1-targeted chemotherapy through their intrinsic DNA repair toolbox.
- Based on these insights, a combination of molecules (the protein PRMT5, and the enzyme TDP1) can be used as potential targets for developing novel anti-cancer therapeutics, thus taking us a step closer to developing precision medicine approaches for cancer patients.
DNA replication:
- Top1, an enzyme in all higher eukaryotes, is essentially responsible for relaxing DNA as it coils during replication (and transcription). The drugs directed at this pathway disrupt the activity of Top1 by changing its shape and rendering it ineffective.
- While these result in a significant amount of cell death, including cancer cells, natural cellular repair mechanisms (using TDP1) often kick in and counteract the action of the drug.
- They developed CRISPR-mediated knock-out cells where the PRMT5 (Protein arginine methyltransferase 5) enzyme in the cells is no longer present.
- When challenged with a low dosage of camptothecin which is below the toleration levels used in chemotherapy, they found that the cancer cytotoxicity increased markedly. This helped confirm that PRMT5 deficiency in the cell is the target of the camptothecin.
Drugs combination for PRMT5:
- The enzyme PRMT5 is broadly overexpressed in many cancer cells. Therefore, targeting the PRMT5 enzyme with drugs in combination with low dosage camptothecin will help in killing cancer cells more effectively.
- The PRMT5 enzyme, which is found in abundance in cancer cells, directly regulates the natural cellular repair mechanisms through chemical finetuning. This results in repairing of DNA breaks generated by camptothecin and thus, resistance to chemotherapy.
- In the last decade, our lab has been investigating DNA repair pathways that offer resistance to camptothecin and its clinical derivatives.
- The objective was to uncover new avenues to kill cancer cells in target-based chemotherapy or personalised chemotherapy using breast and ovarian cancer. They have been using mouse models to further test the combination drug therapy using in vivo tumours.
Major breakthrough:
- In 2018, thye achieved a breakthrough with the identification of the DNA repair proteins TDP1 (Tyrosyl DNA phosphodiesterase 1) and PRMT5 binding which was published in Nucleic Acids Research.
- PRMT5 inhibitor, GSK3326595, has been approved as a monotherapy in phase II clinical trials of cancer. The latest work provides a new rationale for using the combination of Top1-PRMT5 inhibitors in tumorigenesis.
Way Forward:
- Since the rate of proliferation is higher in the case of cancer cells, the chances of combination drug uptake are higher. The personalised approach of combinatorial chemotherapy will effectively kill cancer cells bypassing induced chemoresistance.
- More studies are needed to confirm the lab results, and the end goal is to extend the basic research to human clinical trials to assess the therapeutic potential.
PM launches Power Sector’s Revamped Distribution Sector Scheme
(GS Paper 2, Governance)
Why in news?
- Recently, the Prime Minister participated in the Grand Finale marking the culmination of ‘Ujjwal Bharat Ujjwal Bhavishya – Power @2047’ via video conferencing.
- The grand finale of Ujjwal Bharat Ujjwal Bhavishya organized was a national level celebration where the participants and beneficiaries from over 100 districts across the country were connected through virtual mode.
Revamped Distribution Sector Scheme:
- The Prime Minister launched the Ministry of Power’s flagship Revamped Distribution Sector Scheme which is aimed at improving the operational efficiencies and financial sustainability of Distribution Companies.
Aim:
- With an outlay of Rs.3,03,758 crore over a period of five years from FY 2021-22 to FY 2025-26, the scheme aims to provide financial assistance to DISCOMs for modernization and strengthening of distribution infrastructure, aiming at improvement of the reliability and quality of supply to end consumers.
- It is also proposed to provide 25 crore Smart Prepaid meters to consumers all over the country.
Portal launched:
