Context: Researchers have found that long COVID complications are not correlated with the severity of initial COVID-19. A person can have these complications even after mild or asymptomatic COVID-19 infection.
The study demonstrated a therapeutic strategy to manage COVID. A derivative of the 5B8 antibody has entered phase I clinical trials. If it completes this phase, it is likely to enter phase 2 where researchers will assess clinical endpoints.
SARS-CoV-2 Virus:
- Coronavirus disease 2019 (COVID-19) is a highly contagious viral illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
- SARS-CoV-2 is a novel beta coronavirus belonging to the same subgenus as the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV).
- It was first identified in December 2019 in Wuhan, China, and then caused a global pandemic leading to the COVID-19 pandemic.
- Coronaviruses are positive-stranded RNA viruses with a crown-like appearance due to the presence of spike glycoproteins on the envelope.
- Origin: Although the origin of SARS-CoV-2 is currently unknown, it is widely postulated to have originated from an animal, implicating a zoonotic transmission.
- Transmission: Exposure to respiratory droplets carrying the infectious virus from close contact or droplet transmission from pre-symptomatic, asymptomatic, or symptomatic individuals.
Mechanism of Transmission:
- Entry into the Body: The SARS-CoV-2 virus is primarily transmitted through respiratory droplets or aerosols when an infected person coughs, sneezes, or talks. It can also spread via contact with contaminated surfaces. The virus typically enters the body through the nose, mouth, or eyes and travels down the respiratory tract.
- Binding to Host Cell: SARS-CoV-2 has a characteristic spike protein (S protein) on its surface, which plays a critical role in infection. The spike protein specifically binds to a receptor on the surface of human cells known as ACE2 (Angiotensin-Converting Enzyme 2). These ACE2 receptors are found in high concentrations in the lungs, heart, kidneys, and intestines, which explains why the virus can affect multiple organs.
- Fusion and Entry into the Host Cell:
After binding to the ACE2 receptor, the virus either:
- Fuses with the cell membrane and releases its genetic material directly into the host cell, or
- Enters the host cell through endocytosis, where the cell engulfs the virus, forming a vesicle that brings it inside.
This step is crucial for the virus to inject its RNA into the host cell, initiating the infection process.
- Replication of Viral RNA: SARS-CoV-2 is an RNA virus. Once inside the cell, the virus releases its RNA, which hijacks the host cell’s machinery (ribosomes) to produce viral proteins and replicate the viral RNA. The host cell treats the viral RNA as if it were its own mRNA (messenger RNA), translating it into viral proteins like the spike protein, nucleocapsid, membrane proteins, etc.
- Assembly of New Viruses: Newly made viral proteins and RNA molecules are then assembled into new viral particles (virions) within the host cell. These components come together in special compartments within the cell, like the endoplasmic reticulum and Golgi apparatus, to form complete new viruses.
- Release of New Viruses: Once enough new virus particles are made, they are released from the infected host cell. These new viruses then infect nearby cells, spreading the infection throughout the body.
What is an antibody?
- They are proteins produced by the immune system that neutralise any foreign substance (bacteria, virus) entering the human body.
- An antibody attaches itself to an antigen – a foreign substance, usually a disease-causing molecule – and helps the immune system eliminate it from the body.
What is a monoclonal antibody?
- Monoclonal antibodies are laboratory-made proteins that mimic the behaviour of antibodies produced by the immune system to protect against diseases and foreign substances.
- Monoclonal antibodies are specifically designed to target certain antigens.
How do monoclonal antibodies work?
- Monoclonal antibodies are specifically engineered and generated to target a disease. They are meant to attach themselves to the specific disease-causing antigen. An antigen is most likely to be a protein.
- For example, most successful monoclonal antibodies during the pandemic were engineered to bind to the spike protein of the SARS-CoV-2 virus. The binding prevented the protein from exercising its regular functions, including its ability to infect other cells.