Type: Prelims Only

Why in the News?

Walter Kauzmann’s 1959 idea that protein folding relies on water-loving and water-avoiding parts has now been challenged by new research showing protein cores are more flexible than once believed.

Protein and Protein Folding – Overview

• Proteins: Biological macromolecules made of 20 amino acids in specific sequences.
• Folding: Sequence dictates 3D shape, essential for function.
• Water Interaction:
  • Hydrophilic (e.g., lysine) → outer surface.
  • Hydrophobic (e.g., tryptophan) → buried in core.
• Kauzmann Hypothesis (1959): Proteins have a hydrophobic core and hydrophilic surface, guiding folding.
• 1960s X-ray Evidence: Confirmed hydrophobic residues inside, hydrophilic outside.
• Earlier Belief: Core was highly sensitive—small changes could destabilize protein.

Recent Research:

• Study Design: Tested 78,125 amino acid combos at 7 sites in cores of 3 proteins:
  • Human SH3 domain (FYN tyrosine kinase)
  • Barley CI-2A protein
  • E. coli CspA protein
• Findings:
  • Many changes harmful, but thousands stable (e.g., SH3-FYN had 12,000+ stable conformations).
  • Machine learning accurately predicted stability even with <25% sequence similarity.

Implications:

• Protein Engineering: Core modifications may be possible without losing stability—beneficial for therapeutics.
• Evolutionary Insight: Protein cores may have been more adaptable during evolution than once thought.

Why in the News?

The World Health Organization (WHO) has reclassified hepatitis D virus (HDV) as carcinogenic, following the International Agency for Research on Cancer (IARC) assessment based on data from The Lancet Oncology.

About Hepatitis D:

• What is it: Hepatitis D is a serious liver infection caused by the hepatitis D virus (HDV).
• Cause: Hepatitis D virus (HDV), an incomplete virus needing hepatitis B virus (HBV) for replication.
• Infection Types:
  • Co-infection – HDV + HBV at the same time.
  • Superinfection – HDV infects someone already with HBV.
• Transmission: Parenteral exposure (injections, transfusions), mother-to-child, sexual contact.
• Diagnosis: Blood tests for HDV antibodies and HDV-RNA.
• Prevention: HBV vaccination, safe blood practices, safe sex, screening, avoid needle sharing.

Why Hepatitis D is Carcinogenic?

• Causes more severe liver damage than HBV alone.
• HBV–HDV co-infection raises liver cancer risk 2–6 times compared to HBV-only cases.
• Up to 75% develop cirrhosis within 15 years.
• Can cause cancer even without cirrhosis due to HBV DNA integration + HDV-induced damage.

Why in the News?

With haemophilia care evolving globally, the shift from reactive to preventive treatment has brought Prophylaxis Therapy to the forefront of modern clinical practice.

About Haemophilia:

• What is it: Rare genetic bleeding disorder due to deficiency of clotting factors, mainly Factor VIII (Haemophilia A).
• Effect: Causes prolonged bleeding, even from minor injuries; can lead to internal bleeds in joints, muscles, or brain.
• Key Symptoms: Excessive bleeding, painful joint swelling, risk of disability or brain hemorrhage.
• Prevalence: Estimated 1–1.5 lakh cases in India; only ~29,000 diagnosed (~20%).
• Underdiagnosis Causes: Low awareness, poor access to diagnostics, and socio-economic challenges.
• Impact if Untreated: Each untreated bleed may reduce lifespan by ~16 days; leads to pain, disability, missed school/work, and job loss.

Prophylaxis (Regular Replacement Therapy) and its Benefits:

• What It Is: Regular infusion of clotting factors or non-factor therapies to prevent bleeds.
• Global Standard: Replaces on-demand therapy; adopted as best practice in developed countries.
• Joint Protection: Prevents recurrent bleeds, avoids deformities and long-term disability.
• Quality of Life: Reduces pain and fear, enables normal schooling, work, and social life.
• Healthcare Savings: Cuts emergency visits, hospital stays, and long-term costs.
• Global Status: ~90% of haemophilia patients in developed countries are on prophylaxis.
• India’s Progress: On-demand remains common; some states offer prophylaxis for children under 10.