COVID-19 Antibody Mechanisms Quiz

COVID-19 Treatment and Long-Term Effects

• COVID-19 treatments target the virus directly or the human response to the virus
• Antivirals aim to interfere with the virus's lifecycle, but rapid mutation makes them less effective
• Therapeutic options target host responses, like inflammation, thrombosis, or ARDS
• Repurposed drugs, like dexamethasone and tocilizumab, have shown some effectiveness, but might not be as effective against COVID-19 as originally conceived.
• Vaccines effectively reduce the spread of the virus and hospitalizations and deaths
• Vaccines, such as mRNA and vector types, showed success in mitigating the pandemic
• Common UK approved vaccines include Spikevax (Moderna), Comirnaty (Pfizer/BioNTech), Nuvaxovid (Novavax), Vaxzevria (AstraZeneca/Oxford), Janssen COVID-19 Vaccine (Johnson & Johnson), and Valneva (Valneva)
• Strategies to combat COVID-19 include improved hygiene, distancing, and quarantine or isolation
• The Swiss cheese model illustrates how multiple layers of defense can limit the risk of infection
• Long-term effects of COVID-19 are possible; some may experience lingering symptoms known as Long COVID
• COVID-19 treatment strategies include preventative measures like vaccines, and active/passive immunisation
• COVID-19 treatment strategies also include therapeutic options targeting the virus directly, and host responses
• Long COVID is considered a long-term effect for some, but symptoms differ widely among individuals
• Data on vaccination, positive cases, deaths, and hospitalizations are compiled for the UK and presented to track the trends

Principles of Virus Infection Control

• Removing virus reservoirs (e.g., animals carrying zoonotic viruses)
• Interrupting transmission (e.g., hygiene, masks, lockdowns)
• Enhancing host resistance (e.g., vaccines, vitamin C)

Therapies Targeting Host Response or Virus

• Inflammation control with immunosuppressants
• Blood clotting management with anticoagulants
• Acute Respiratory Distress Syndrome (ARDS) support
• Regulating the renin-angiotensin-aldosterone system (RAAS)
• Various antibodies and therapies to target the virus directly, and target the host response to the virus.

Antivirals

• Antibiotics are ineffective against viruses
• Approximately 40 licensed antivirals exist
• Antivirals target a limited number of known viruses
• Some antivirals, such as nirmatrelvir/ritonavir (Paxlovid) and remdesivir, are used for COVID-19 treatment

COVID-19 Antiviral Targets

• Viral targets exist for antiviral discovery, including various enzymes and proteins utilized during viral processes
• Current targets for direct-acting SARS-CoV-2 antiviral therapeutics

Targeting the Viral Lifecycle- Entry

• Antibodies can be developed to hinder viral entry
• Various antibodies (e.g., monoclonal antibodies) are generated to target spike proteins and/or RBD
• The spike protein's binding to ACE2 for entry is a frequent therapeutic target.
• Various technologies are being implemented to improve the targeting of drugs at the viral protein level.

Targeting the Viral Lifecycle - Polyprotein Processing

• NSP3 (PLpro) and NSP5 (Mpro), cysteine proteases that cleave and/or release proteins from the viral polyprotein, are popular targets as they've shown to have similar functionalities to human enzymes
• The high similarity with host enzymes makes these viral proteases difficult drug targets

Targeting the Viral Lifecycle - Replication

• The enzymes associated with viral RNA Replication and capping are potential targets for therapies
• Targeting the RdRp (RNA-dependent RNA polymerase) and the enzymes in the process of RNA replication and capping
• Many enzymatic activities associated with viral RNA replication allow for numerous targets
• Various therapies are aimed at viral RNA replication and capping process
• Drugs such as Remdesivir, Molnupiravir, and others target the RNA polymerase stage

Targeting the Viral Lifecycle – Polymerase

• Nucleos(t)ide analogues cause premature termination, and can lead to mutagenic changes in the virus
• Non-nucleos(t)ide analogues hinder the binding of RdRp to the RNA template strand.
• Remdesivir and Molnupiravir are examples of drugs targeting the viral RNA polymerase
• Many other drugs based on these principles are under development

Targeting the Viral Lifecycle- Remdesivir

• It is a prodrug that is activated after uptake by cells in the body
• It was developed against other respiratory viruses and has some utility against SARS-CoV-2, and can improve recovery from infections.

Targeting the Viral Lifecycle- Molnupiravir

• Molnupiravir causes mutagenic incorporation in new viral RNA, and was recently approved
• Its efficacy and benefit over standard care is still uncertain

Targeting the Viral Lifecycle - Summary

• A variety of methods and principles target different stages in the COVID-19 viral lifecycle

Current COVID Situation in England

• Data on vaccination, positive cases, deaths, and hospitalizations are compiled for the UK and presented to track the trends

Vaccination

• Various vaccines (mRNA, vector, and subunit, inactivated) have been developed, along with their protocols for different age groups and timing.

Vaccines - Current UK Approved

• The names of six approved vaccines for the UK have been provided
• The presentations include graphic representations of the vaccination schedules
• The presentation also discusses the efficacy of various vaccines in relation to various SARS-CoV-2 variants

Vaccines- Mechanisms

• The mechanisms of different vaccines' functionalities are explained

Stabilized in Prefusion Conformation

• The presented process discusses how two proline residues enhance a stability difference in spike protein conformation
• This is important because the incoming virus particles do not have these residues

Conclusion

• The efficacy and longevity of the presented strategies and technologies (therapeutic, preventive, etc.) against the COVID-19 virus are under review
• The current COVID situation in England is being tracked through various metrics.