sars virus ( severe acute respiratory syndrome).

SARS (Severe Acute Respiratory Syndrome) is a viral respiratory illness caused by the SARS-CoV coronavirus. It emerged in 2002-2003, leading to a global outbreak. The virus spreads through respiratory droplets and causes symptoms like fever, cough, and difficulty breathing. In severe cases, it can lead to pneumonia and respiratory failure. SARS was controlled through public health measures, but there is no specific antiviral treatment for it.

1. S.NAHIDHA BEGUM II –M.Sc Microbiology Department of Microbiology Sacred Heart College Severe Acute Respiratory Syndrome ( SARS VIRUS )

2. INTRODUCTION WHAT IS SARS? SARS, or Severe Acute Respiratory Syndrome , is a highly contagious respiratory illness caused by the SARS- CoV virus. It can lead to severe pneumonia and respiratory failure . classification of the SARS virus (SARS-CoV) is as follows: Order : Nidovirales Family : Coronaviridae Genus : Betacoronavirus Species : Severe acute respiratory syndrome-related coronavirus (SARSr-CoV)

3. STRUCTURE OF SARS VIRUS Lipid Envelope: The virus is surrounded by a lipid envelope derived from the host cell membrane, which is studded with viral spike (S) proteins. spike protein (S): glycoprotien helps in binding to ACE2 receptor of the host and facilitate entry Nucleocapsid (N): Bound to RNA genome forms nucleocapsid Membrane protein (M): central organizer of CoV assembly, determines shape of viral envelope Envelope protein(E): interacts with membrane protein to form viral envelope RNA Genome :SARS-CoV has a positive-sense, single-stranded RNA genome.

4. REPLICATION OF SARS VIRUS Virus Entry : SARS-CoV-2 enters host cells through endosomes or plasma membrane fusion. Spike Protein and ACE2 Interaction : Spike proteins (S1, S2) mediate attachment to the host cell membrane. ACE2 serves as the entry receptor for viral engagement. Inhibitors: Griffithsin (Inhibitor III) prevents viral entry by binding to the spike glycoprotein. Exogenous heparin competes with heparan sulfate (HS) for SARS-CoV-2 S protein binding, inhibiting viral adhesion.- Co-Receptor and Enhancement: Cell surface vimentin (VIM) acts as a critical co-receptor for successful ACE-2 binding. Heparan sulfate (HS) binding to the receptor binding domain (RBD) enhances ACE2 binding.

5. Endosomal Entry Activation : Cathepsin L activates spike protein in endosomes. Lysosomotropic agents like bafilomycin A1 or ammonium chloride (Inhibitor Classes IV,V) block the pH-dependent cysteine protease. Plasma Membrane Fusion: TMPRSS2, a cellular serine protease, cleaves spike protein between S1 and S2 domains. Fusion of viral membrane with plasma membrane is initiated, promoting efficient viral replication. Antiviral Immunity Consideration: Plasma membrane fusion entry is less likely to trigger host cell antiviral immunity, making it more efficient for viral replication Translation of Viral Replication Machinery (2) and Replication (3) : Viral RNA release into host cell initiates polyprotein translation. Coronavirus genomic RNA encodes nonstructural proteins (NSPs) and structural proteins.- Polyproteins pp1a and pp1ab are initially translated. Cleaved by Papain-like protease (PLpro, Nsp3) and 3C-like protease (3CLpro, Nsp5) to form functional NSPs Functional NSPs, including Helicase and RdRp, play crucial roles in viral RNA synthesis. RdRp is a target for inhibitors like Favipiravir or Penciclovir (Inhibitor VI) Replication of viral RNA can be inhibited by kinase signaling pathway inhibitors like Saracatinib (Inhibitor VII).

6. N protein expression level can be reduced by resveratrol (Inhibitor X). Host shutoff factor Nsp1, one of the first translated proteins, interferes with translation and accelerates degradation of host mRNA. This suppression of host mRNA helps the virus evade the host's innate immune response. Translation of Viral Structure Proteins (4) and Virion Assembly (5) : RdRp (Nsp12) orchestrates the replication of structural protein RNA. Structural proteins S, Envelope (E), and Membrane (M) are translated by ribosomes attached to the endoplasmic reticulum (ER). The ER forms double membrane vesicles (DMVs) where viral RNA replication occurs, shielding it from the host's innate immune system. Nsp3 creates pores facilitating the exit of viral RNA from DMVs for virion assembly. Nucleocapsid proteins (N) stay in the cytoplasm and are assembled from genomic RNA. Nucleocapsids fuse with the virion precursor, and the assembly is transported from the ER through the Golgi Apparatus. The transportation to the cell surface is facilitated by small vesicles. This organized process culminates in the assembly of mature virions, ready for release.

7. Release of Virus (6) Virions are released from infected cells via exocytosis to search for another host cell. Oseltamivir inhibits neuroamidase, preventing cleavage of sialic acids from cell receptors and hindering virion release (Inhibitor XI). SARS-CoV-2 has a distinctive feature, a second cleavage site in the S protein, setting it apart from other coronaviruses. Furin cleavage at the S1/S2 site likely occurs during virion release through the Golgi apparatus or lysosomes.- This primes the S protein for a second cut at the S2’ site by TMPRSS2. Mutations in the S2’ site are associated with SARS-CoV-2 variants of concern: alpha (B.1.1.7), beta (B.1.351), delta (B.1.617.2), and omicron (B.1.1.529).

8. Mode of transmission : Airborne : ️ Virus spreads through droplets and aerosols. Close contact : Virus can spread through touch and close proximity. Fomite transmission : Virus can be deposited on surfaces and objects.

9. PATHOGENESIS OF SARS VIRUS Virion Structural Proteins: SARS-CoV-2 virion comprises S (spike), N (nucleocapsid), M (membrane), and E (envelope) proteins.- Infection Stages: Stage 1 (Attachment ): S protein (S1 domain) binds to ACE2 receptor on the host cell. Stage 2 (Cleavage): TMPRSS2 cleaves the S protein. - Stage 3 (Activation): Cleavage activates the S2 domain for fusion. - Stage 4 (Fusion) : Activated S2 fuses viral and host lipid bilayers, depositing the viral RNA genome into the host cell. Viral Replication : Replication produces double-stranded RNA (dsRNA) intermediates.- Innate Immune Sensing: dsRNA activates MDA5 or RIG-I, initiating a signaling cascade through MAVS. Interferon Response: Signaling leads to the production of type I and type III interferons (IFNs). IFNs act in a paracrine and autocrine manner via plasma membrane receptors. - JAK–STAT1/2 signaling cascade is triggered. Results in the production of interferon-stimulated genes (ISGs) with antiviral functions. Specific Structures :- DMV (double-membrane vesicle) involved in viral replication. ISRE (interferon-sensitive response element) associated with interferon response.

10. CLINICAL SIGNS AND SYMPTOMS Late Symptoms Dry cough shortness of breath difficulty breathing . Pneumonia acute respiratory distress syndrome acute cardiac injury acute renal failure encephalitis Hypotension Complications Fever headache muscle aches respiratory symptoms Early Symptoms 2-10 days Incubation Period

11. LABORATORY DIAGNOSIS Nucleic Acid Testing (NAT): - RT-PCR (Reverse Transcription Polymerase Chain Reaction) detects viral RNA. - Real-time RT-PCR allows quantification of viral load. Serological Tests - Detect antibodies (IgM, IgG) against SARS virus. ELISA and rapid tests are common methods. Immunofluorescent assay (IFA)

12. TREATMENT Severe cases require intensive support. Ribavirin Lopinavir/Ritonavir Systemic corticosteroids Prevention and Control Measures Wear a mask and practice hand hygiene.   Avoid contact with infected individuals.  Isolate if sick or exposed Limit large gatherings and travel.  Implement rapid testing and contact tracing.  Provide medical care and resources

13. REFERENCES : https://www.antibodies-online.com/resources/18/5410/sars-cov-2-life-cycle-stages-and-inhibition-targets / https://www.physio-pedia.com/SARS_Severe_Acute_Respiratory_Syndrome https://www.nature.com/articles/s41579-022-00713-0/figures/1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1829448/ https://www.slideshare.net/ShubhangiHedau/severe-acute-respiratory-syndrome-sars-251254476 https://www.who.int/health-topics/severe-acute-respiratory-syndrome#tab=tab_1 https://radiopaedia.org/articles/severe-acute-respiratory-syndrome-1?lang=us https://bestpractice.bmj.com/topics/en-us/904/epidemiology

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