Antiviral agents Flashcards
Antiretroviral drugs have been covered in the deck for Retroviruses.
Name Herpesviruses for which antiviral agents have been developed, and also classify the antiviral agents by mechanism of action.
(a) Herpes Simplex Virus (HSV)
💊 DNA Polymerase Inhibitors: Acyclovir, Valacyclovir, Famciclovir
(b) Varicella-Zoster Virus (VZV)
💊 DNA Polymerase Inhibitors: Acyclovir, Valacyclovir, Famciclovir
(c) Cytomegalovirus (CMV)
💊 DNA Polymerase Inhibitors: Ganciclovir, Valganciclovir, Cidofovir.
💊 Non-Nucleoside Inhibitors: Foscarnet (inhibits viral DNA polymerase).
(d) Epstein-Barr Virus (EBV)
💊 Limited specific treatment: Acyclovir (DNA polymerase inhibitor) may have minor benefit.
Name Hepatitis viruses for which antiviral agents have been developed, and also classify the antiviral agents by mechanism of action.
(a) Hepatitis B Virus (HBV)
💊 Reverse Transcriptase Inhibitors: Tenofovir, Entecavir
💊 Interferons: Pegylated Interferon alfa (enhances host immune response)
(b) Hepatitis C Virus (HCV)
💊 RNA Polymerase Inhibitors: Sofosbuvir
💊 NS5A Inhibitors: Ledipasvir, Velpatasvir (inhibit viral replication complex)
💊 Protease Inhibitors: Glecaprevir, Grazoprevir (block viral protein processing)
Name antiviral agents used against Influenza A and B, and also classify the antiviral agents by mechanism of action.
💊 Viral release inhibitors: Oseltamivir, Zanamivir (neuraminidase inhibitors)
💊 RNA polymerase inhibitors: Baloxavir, Marboxil (inhibits cap-dependent endonuclease activity).
Name antiviral agents used against SARS-CoV-2, and also classify the antiviral agents by mechanism of action.
💊 RNA Polymerase Inhibitors: Remdesivir, Molnupiravir
💊 Protease Inhibitors: Paxlovid (Nirmatrelvir/Ritonavir)
💊 Monoclonal Antibodies: Sotrovimab, Tixagevimab/Cilgavimab (neutralize spike proteins)
Name antiviral agents used against Poxviruses, and also classify the antiviral agents by mechanism of action.
(a) Variola Virus (Smallpox)
DNA Polymerase Inhibitors: Tecovirimat, Cidofovir, Brincidofovir
(b) Monkeypox Virus
DNA Polymerase Inhibitors: Tecovirimat
Name antiviral agents used against Respiratory Syncytial Virus, and also classify the antiviral agents by mechanism of action.
💊 RNA Synthesis Inhibitor: Ribavirin
💊 Monoclonal Antibodies: Palivizumab (binds to fusion protein to prevent viral entry)
Name antiviral agents used against hemorrhagic fever viruses and classify the antiviral agents by mechanism of action [Ebola, Lassa].
(a) Ebola Virus
💊 RNA Polymerase Inhibitors: Remdesivir
💊 Monoclonal Antibodies: Inmazeb (targets viral glycoproteins)
(b) Lassa Virus
💊 RNA Synthesis Inhibitor: Ribavirin (off-label)
What is the first line regimen for treatment of HIV in Kenya?
2 NRTI’s: Lamivudine, Tenofovir
1 Integration inhibitor: Dolutegravir
Describe the mechanism of action of acyclovir.
(1) Acyclovir is a guanosine analog activated by viral thymidine kinase in infected cells.
(2) It is converted to acyclovir triphosphate, the active form, by cellular enzymes.
(3) Acyclovir triphosphate preferentially inhibits viral DNA polymerase over host DNA polymerase.
(4) It inhibits DNA replication via chain termination
(5) Selectivity for infected cells minimizes adverse effects on uninfected cells.
Briefly discuss the mechanism of action of monoclonal antibodies in the treatment of Covid-19.
Monoclonal antibodies were designed to bind to the spike proteins of SARS-CoV-2 which is responsible for the entry of the virus into human cells, the antibodies prevent the virus from attaching to the ACE2 receptor on human cells blocking the virus from entering the body.
Briefly discuss the mechanism of action of pegylated interferon in the treatment of Hepatitis B and C.
💊 Pegylated interferon is a modified interferon with a polyethylene glycol (PEG) attached. This modification enhances its stability and prolongs its half-life in the body, allowing for less frequent dosing compared to non-pegylated interferons.
💊 It activates the JAK-STAT (Janus kinase-signal transducer and activator of transcription) pathway on the surface of target cells which in turn increases expression of multiple genes in multiple tissues involved in the innate antiviral response.
Differentiate the mechanism of action of nucleoside-reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors.
NRTI: Competitively inhibit nucleotide binding to reverse transcriptase and terminate the DNA chain through chain termination. [Note: Tenofovir is a nucleoTide; the others are nucleosides.]
NNRTI’S: Bind to reverse transcriptase at site different from NRTIs. Do not require phosphorylation to be active or compete with nucleotides.
Outline the pan-genotypic regimen(s) of treating Hepatitis C.
(a) NS5A inhibitors: Ledipasvir, Ombitasvir, Velpatasvir
Inhibits NS5A, a viral phosphoprotein that plays in RNA replication; exact mechanism unknown
(b) NS5B inhibitors: Sofosbuvir, Dasabuvir
Inhibits NS5B, an RNA-dependent RNA polymerase acting as a chain terminator.
Prevents viral RNA replication
(c) NS3/4A inhibitors: Grazoprevir, Simeprevir
Inhibits NS3/4A, a viral protease, preventing viral replication
(d) Ribavirin
Inhibits synthesis of guanine nucleotides by competitively inhibiting IMP dehydrogenase
What are the benefits of antiviral combination therapy?
(1) Enhanced therapeutic efficacy through additive and synergistic effects, leading to improved clinical outcomes and dramatic reductions in viral load, morbidity, and mortality rates.
(2) Reduced likelihood of drug resistance development, as viruses are less likely to develop resistance to multiple drugs simultaneously. This is particularly important for rapidly mutating viruses like influenza.
(3) Improved quality of life and increased lifespan for patients with chronic viral infections, such as HIV and HCV, where combination therapy has become the standard of care.
(4) Better treatment options for patients with comorbidities or those who have relapsed after initial treatment. For example, new drug combinations have achieved high success rates in drug-experienced HCV patients.
(5) Faster recovery times, as demonstrated in studies showing combination therapies like Remdesivir and Baricitinib reduced recovery time compared to monotherapy while also leading to fewer adverse events.
