Molecular Medicine

• Patients are the main source of infection for COVID-19
• true or false. COVID is a self-limiting disease
• main transmission routes of covid

  • respiratory droplets, airborne, contact transmission
• basic reproduction number (R0) of COVID– 2.2
• The average incubation period of COVID – 5 days
• Most common Symptoms of COVID

  • fever (98%)
  • cough (76%)
  • myalgia or fatigue (44%)
  • Dyspnea
• Two Distinct SARS-CoV-2 Entry Pathways:

  Endosomal

  Cell surface
• S protein is cleaved into s1 and s2 by furin in golgi apparatus
• which bind to the receptor in Golgi apparatus for dengue?

  S2
• COVID entry Pathways:

  Endosomal : ACE2 Receptors

  Cell Surface: TMPRSS2 Receptors
• • possesses a nucleocapsid composed of genomic RNA and phosphorylated nucleocapsid (N) protein
  • phospholipid bilayers with two different types of spike proteins
  • the spike glycoprotein trimmer (S) that exists in all CoVs
  • hemagglutinin-esterase (HE) only shared among some CoVs
  • membrane (M) protein
  • envelope (E)

  
• Gold Standard Diagnosis for COVID

  • Nucleic acid test
• if you have symptoms, what test is recommend for COVID?

  
  

  • antigen test
• Diffuse Alveolar Damage (DAD)

  • Impaired cell function, followed by cell death (necrosis or apoptosis, exudates, desquamation of pneumocytes, and formation of hyaline membranes, which are characteristic of
• • Imaging of COVID – patchy shadows or ground glass appearance
  • Chest x-ray
  • CT scan
• Vaccines against COVID

  Inactivated whole virus - SINOVAC

  Protein subunit nanoparticle - NOVACIN

  Adenoviral Vector - Astrazeneca

  mRNA-LNP- Pfizer & Moderna
• NONSEVERE

  
  

  Most Recommended Drug:

  Nirmatrelvir (inhibits major protease)

  Ritonavir (inhibits cytochrome 3a4 to prolong the activity of Nirmatrelvir)

  (EX: Pfizer and Paxlocin) - first 5 days!!!

  
  

  Molnupiravir (found in Mercury drug HAHA) - but requires mitigation strategies to reduce potential harms
• SEVERE

  Most Recommended Drug: Corticorsteroid, IL-6 receptor Blockers, Barcitinib (all 3 may be combined)
• Protein E (Dengue)

  • Most important structural protein
  • Binding of virus and cell receptors
  • Fusion of viral envelope and cell membrane
  • Main virulence and antigenic protein of the virus

  
• Protein C

  • Specific antigen determinant
  • Does not induce antibody production !!
  • Assembly and virus replication
  • Induce apoptosis
  • Regulating inflammatory cytokines
• Protein M (Dengue)

  • Can mediate the fusion of E protein and cell membrane

  
• Protein C

  • Specific antigen determinant
  • Does not induce antibody production !!
  • Assembly and virus replication
  • Induce apoptosis
  • Regulating inflammatory cytokines

  
• • NS1
  • Present on surface of infected cell
  • Can induce autoimmune response
• • N2A
  • Regulate interferon pathway
• • NS2B and NS3
  • Forms a functional complex to exert proteolytic activity
• • NS4A and NS4B
  • Regulate IFN signal transduction
• • NS5
  • Largest and most conserved protein
  • Inhibits the interference of RNA Pathway
  • Closely related to pathogenicity of the virus
• Dendritic cells (DCs)

  • Connection between innate and adaptive response
  • Up-regulation of pro-inflammatory cytokines and co-stimulatory molecules that help activate immune system
  • Extends antigen to the T cells in the draining Lymph nodes
  • Migration and Maturation interfered by NS1 through regulation and of gene related expression
• Activated skin Mast cells

  • Activate recruitment of cytotoxic T cells
  • CD8, NK and NKT
• CD8

  • Terminate infected cells directly
  • NS3 viral protein identification w/ help of CD4
• CD4

  • Capsid, envelope, NS1 epitopes
  • B cell response, extracting memory response from CD8 T cells
• Complement System

  • Block virus in early stage
  • Evasion by NS1
• IFN

  • First line of defense
  • Control viral replication in early stage
• TLRs and C-type lectin receptors

  • PRR – Pattern recognition receptors
  • Virus enters skin activates PRRs in turn will activate antiviral immune response
  • IFNs and TNF
• Activation of TLR-3 and TLR-7

  • IFN-a and IFN-b
• Intracellular sensors

  • RIG-1 and MDA5
  • Viral recognition
  • IFN-b
• True or False. Non-neutralizing antibody against DENV further enhances the infectivity of the virus
• Cytokine Storm

  • Induces rapid and massive production of cytokines
  • hemmoraghic fever
• DENV Diagnosis

  Primary Dengue Infection

  -NS1: increase where the patient is febrile

  -IgM: increase 1st

  -IgG: increase 2nd

  
• DENV Diagnosis

  Secondary Dengue Infection

  -NS1: decrease because of memory cells

  -IgG: increase 1st

  -IgM: increase 2nd