SARS-CoV-2 (COVID-19)

Family

Coronaviridae

Genome

• Positive-sense, ssRNA

• Non-segmented, ~30 kb

• Encodes 27 proteins

Zoonotic origin

• Likely from bats

• Intermediate hosts involved (e.g., pangolins, possibly others)

• SARS & MERS use different receptors

Structural Proteins (in virion)

SEMN

• spike

• envelope

• membrane

• nucleocapsid

Spike

Entry (binds ACE2), host tropism, major vaccine target, neutralizing

Envelope

Smallest protein; assembly, release

Membrane

Most abundant; shape and assembly

Nucleocapsid

Encapsulates RNA; transcription efficiency, immunogenic

Non-Structural Proteins (NSPs)

• Form Replication-Transcription Complex (RTC)

• Translated from pp1a & pp1ab (polyproteins)

• Cleaved by PLpro and 3CLpro

• Example: nsp14 → proofreading

Accessory Proteins

• Not in virion; found in infected cells only

• Examples: ORF3b, ORF6, ORF7a

Replication cycle: Attachment and entry

• Spike binds ACE2

• Two routes:

  • ACE2 + TMPRSS2 (e.g., Delta)

  • Endocytosis (e.g., Omicron)

• TMPRSS2 cleaves S at S1/S2 + S2' sites → promotes entry

Replication cycle: Replication

• (+)ssRNA used directly to make proteins

• pp1a, pp1ab → cleaved into NSPs

• RTC assembles → viral RNA synthesis

Replication cycle: Assembly and release

• In ER-Golgi vesicles

• Viral RNA + S, E, M, N proteins assembled → exocytosed

Immune response: Systemic immunity

IgG, T cells (CD4+, CD8+) in blood

Immune response: Mucosal immunity

IgA, local T cells (lung, nasal, saliva)

Immune response: Adaptive immunity sites

Lung, oral cavity, nasal passages

Vaccines & Immune Targets

• Focus on Spike (S) protein

• Induce neutralizing antibodies

• Target both systemic & mucosal immunity

Phylogenetics & Variants

• Use sequence analysis & similarity plots to trace origin

• Bats have >500 CoVs in China

• Delta: TMPRSS2 route, more lung infection

• Omicron: Endocytosis route, more upper airway infection

Transmission

• Droplets, aerosols, fomite (smear)

• Masks: reduce airborne transmission

• Higher transmission in enclosed spaces

Monoclonal Ab / Convalescent Plasma

• Block ACE2 binding

• Targets entry

Camostat Mesylate

• Inhibits TMPRSS2

• Targets entry

Lopinavir/Ritonavir

• HIV protease inhibitors

• Targets viral protease

Remdesivir

• RNA synthesis inhibitor

• Targets RdRp

Ribavirin

• May inhibit mRNA capping

• Targets RNA synthesis

Chloroquine/Hydroxychloroquine

• Interferes with progeny release

• Targets exit

key features summary

• +ssRNA, non-segmented (~30 kb)

• Uses ACE2 (Delta: TMPRSS2 / Omicron: endocytosis)

• Spike protein = target for vaccines and neutralizing antibodies

• Replicates in cytoplasm using RTC

• Transmission: droplets, aerosol

• Treatments target entry, replication, or protease activity