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Corona viruses- Latest research findings
What is known??
What lies ahead??
Transmission electron microscope image shows SARS-CoV-2, the virus
that causes COVID-19, isolated from a patient in the U.S. Virus particles
are emerging from the surface of cells cultured in the lab. The spikes on
the outer edge of the virus particles give coronaviruses their name,
crown-like. Ref. https://www.nih.gov/news-events/nih-research-matters/novel-
coronavirus-structure-reveals-targets-vaccines-treatments
Prepared by
Pritam Bardhan
Research Scholar,
Department of Molecular Biology & Biotechnology , Tezpur University
Myotis sp.
Rhinolophus sp.
Asian palm civet (Paradoxurus hermaphroditus)
(Natural reservoir)
(Interim reservoir)
Humans-unfortunate victims
Really??
Fan et al. (2019) Bat Coronaviruses in China, viruses
Picture of Wuhan sea food market
Live slaughtered animals are more nutritious- Chinese food culture
World Health Organization (WHO) has declared novel corona virus (COVID-19) outbreak a
“pandemic” on 09th March, 2020
Structure of respiratory syndrome causing human
corona viruses
Shereen et al. (2020)"COVID-19 infection: origin, transmission, and characteristics of human coronaviruses." Journal of
Advanced Research ; Fan et al. (2019) Bat Coronaviruses in China, viruses
Key points:
 CoV genome is a positive
sense single-strand RNA
(+ssRNA), 27–32 kb in size
 Two-thirds of genomic RNA
encodes for viral polymerase
(RdRp) and other non-structural
proteins involved in RNA
synthesis or host response
modulation
 one third of the genome
encodes for structural proteins-
spike, envelope, membrane
glycoprotein and nucleocapsid
Two large overlapping polyproteins (ORF1a/ORF1b) which are precursor of viral polymerase
and the four structural proteins are relatively consistent, the length of the CoV genome is
dependent on the number and size of accessory proteins
Corona viruses-Baltimore group-IV; Family-Coronaviridae
Life cycle of SARS CoV-2 inside human cell
 Spike (S) proteins binds to
cellular receptor ACE2
(angiotensin-converting
enzyme-2)
 receptor binding brings
about conformational
changes in S protein that
facilitates fusion of viral
envelope with cell membrane
through the endosomal
pathway
 SARS CoV-2 RNA is
released into the host cell
 genome RNA is translated
into viral replicase
polyproteins, cleaved into
small products by viral
proteinases
 The polymerase produces a series of subgenomic mRNAs by discontinuous transcription
which are finally translated into viral proteins
 viral proteins and genome RNA are assembled into virions in the ER and Golgi and
transported via vesicles and released out of the cell
Shereen et al. (2020)"COVID-19 infection: origin, transmission, and characteristics of human coronaviruses." Journal of Advanced Research
Phylogenetic analysis of coronaviruses from different species and 2019 novel coronavirus in China; SARS-
CoV-2 was closely related to coronaviruses derived from five wild animals (Paguma larvata, Paradoxurus
hermaphroditus, Civet, Aselliscus stoliczkanus and Rhinolophus sinicus); Highest homology with bat
coronavirus isolate RaTG13 (based on complete genome and ORF1a homology 93.7 % and 96.5 %
respectively)-suggesting that the virus is not the same coronavirus as coronaviruses derived from these
five animals
Li et al. (2020) Genetic evolution analysis of 2019 novel coronavirus and coronavirus from other species. Infection, Genetics and Evolution,
p.104285.
Tracing the Evolutionary relationship of novel coronavirus (SARS-CoV-2
Phylogenetic tree of coronaviruses showing the relationship of Wuhan-Hu-1 (causing Wuhan seafood market pneumonia)
to selected coronavirus based on complete genome nucleotide sequence. The viruses are grouped into four genera ;
Alphacoronavirus, Betacoronavirus, Gammacoronavirus and Deltacoronavirus . The tree was reconstructed with sequences
of the complete RNA- dependent RNA polymerase- coding region of the representative novel coronaviruses
Shereen et al. (2020)"COVID-19 infection: origin, transmission, and characteristics of human coronaviruses." Journal of Advanced Research
Phylogenetic Relationship of CoVs Based on the Whole Genome and RdRp Gene Nucleotide Sequences
Pangolin-CoV, RaTG13, and SARS-CoV-2 were clustered into a well-supported group, here named the “SARS-
CoV-2 group
Zhang et al. (2019). Probable Pangolin Origin of 2019-nCoV Associated with Outbreak of COVID-19. Current Biology
Comparison of complete genome organization similarity among SARS-CoV-2, Pangolin-CoV
(91.02 %), and BatCoV RaTG13 (93.7 %).
Considering the wide spread of SARSr-CoVs in natural reservoirs, such as bats, camels,
and pangolins, these findings would be meaningful for finding novel intermediate SARS-CoV-2
hosts to block interspecies transmission.
Zhang et al. (2019). Probable Pangolin Origin of 2019-nCoV Associated with Outbreak of COVID-19. Current Biology
Amino acid sequence alignment of S1 protein and its phylogeny
S1 protein of Pangolin-CoV is more closely related to that of 2019-CoV than to that of RaTG13. Within the
RBD, we further found that Pangolin-CoV and SARS-CoV-2 were highly conserved, with only one amino acid
change (500H/500Q)
Zhang et al. (2019). Probable Pangolin Origin of 2019-nCoV Associated with Outbreak of COVID-19. Current Biology
Tracing the transmissibility and pathogenicity determinant
The S1/S2 cleavage site in the S protein is also an important determinant of the transmissibility and pathogenicity of SARS-
CoV/SARS-CoV viruses.
Four amino acid insertions (SPRRs) unique to SARS-CoV-2
SARS-CoV-2 S protein contains putative furin recognition motif (PRRARSV) similar to that of MERS-CoV, which has a
PRSVRSV motif. The furin sequence motif at the S1/S2 site is missing in the S protein of Pangolin-CoV and all other
SARS/SARSr-CoVs
Zhang et al. (2019). Probable Pangolin Origin of 2019-nCoV Associated with Outbreak of COVID-19. Current Biology
S proteinHost cell
proteases
cleave at
S1/S2
cleavage site
N-terminal S1
ectodomain
C-terminal S2
membrane anchored
protein
(Recognize
cell surface
receptor)
(drives fusion of viral
envelope with cell
membrane)
This difference indicates the
SARS-CoV-2 might gain a
distinct mechanism to promote
its entry into host cells
Key research questions ??
 why there are so many genetically divergent CoVs in bats? (Linked to the diversity
of bat species)
 What is the pathogenesis of most bat CoVs in humans? (Bottleneck: Isolation and
identification of viruses from bats that pose a threat to humans apart from those
viruses that were identified during the outbreaks)
 What is the mechanism of disease transmittance? (For e.g. SARS CoV & SADS
CoV were transmitted from bats to humans or swine; there exact transmission routes
are unknown)
 Bats as a natural reservoir of corona viruses (CoV), how can bats maintain CoVs
long-term without showing clinical symptoms of diseases?
Fan et al. (2019) Bat Coronaviruses in China, viruses
Corona virus latest research findings

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Corona virus latest research findings

  • 1. Corona viruses- Latest research findings What is known?? What lies ahead?? Transmission electron microscope image shows SARS-CoV-2, the virus that causes COVID-19, isolated from a patient in the U.S. Virus particles are emerging from the surface of cells cultured in the lab. The spikes on the outer edge of the virus particles give coronaviruses their name, crown-like. Ref. https://www.nih.gov/news-events/nih-research-matters/novel- coronavirus-structure-reveals-targets-vaccines-treatments Prepared by Pritam Bardhan Research Scholar, Department of Molecular Biology & Biotechnology , Tezpur University
  • 2. Myotis sp. Rhinolophus sp. Asian palm civet (Paradoxurus hermaphroditus) (Natural reservoir) (Interim reservoir) Humans-unfortunate victims Really?? Fan et al. (2019) Bat Coronaviruses in China, viruses
  • 3. Picture of Wuhan sea food market Live slaughtered animals are more nutritious- Chinese food culture
  • 4. World Health Organization (WHO) has declared novel corona virus (COVID-19) outbreak a “pandemic” on 09th March, 2020
  • 5. Structure of respiratory syndrome causing human corona viruses Shereen et al. (2020)"COVID-19 infection: origin, transmission, and characteristics of human coronaviruses." Journal of Advanced Research ; Fan et al. (2019) Bat Coronaviruses in China, viruses Key points:  CoV genome is a positive sense single-strand RNA (+ssRNA), 27–32 kb in size  Two-thirds of genomic RNA encodes for viral polymerase (RdRp) and other non-structural proteins involved in RNA synthesis or host response modulation  one third of the genome encodes for structural proteins- spike, envelope, membrane glycoprotein and nucleocapsid Two large overlapping polyproteins (ORF1a/ORF1b) which are precursor of viral polymerase and the four structural proteins are relatively consistent, the length of the CoV genome is dependent on the number and size of accessory proteins Corona viruses-Baltimore group-IV; Family-Coronaviridae
  • 6. Life cycle of SARS CoV-2 inside human cell  Spike (S) proteins binds to cellular receptor ACE2 (angiotensin-converting enzyme-2)  receptor binding brings about conformational changes in S protein that facilitates fusion of viral envelope with cell membrane through the endosomal pathway  SARS CoV-2 RNA is released into the host cell  genome RNA is translated into viral replicase polyproteins, cleaved into small products by viral proteinases  The polymerase produces a series of subgenomic mRNAs by discontinuous transcription which are finally translated into viral proteins  viral proteins and genome RNA are assembled into virions in the ER and Golgi and transported via vesicles and released out of the cell Shereen et al. (2020)"COVID-19 infection: origin, transmission, and characteristics of human coronaviruses." Journal of Advanced Research
  • 7. Phylogenetic analysis of coronaviruses from different species and 2019 novel coronavirus in China; SARS- CoV-2 was closely related to coronaviruses derived from five wild animals (Paguma larvata, Paradoxurus hermaphroditus, Civet, Aselliscus stoliczkanus and Rhinolophus sinicus); Highest homology with bat coronavirus isolate RaTG13 (based on complete genome and ORF1a homology 93.7 % and 96.5 % respectively)-suggesting that the virus is not the same coronavirus as coronaviruses derived from these five animals Li et al. (2020) Genetic evolution analysis of 2019 novel coronavirus and coronavirus from other species. Infection, Genetics and Evolution, p.104285. Tracing the Evolutionary relationship of novel coronavirus (SARS-CoV-2
  • 8. Phylogenetic tree of coronaviruses showing the relationship of Wuhan-Hu-1 (causing Wuhan seafood market pneumonia) to selected coronavirus based on complete genome nucleotide sequence. The viruses are grouped into four genera ; Alphacoronavirus, Betacoronavirus, Gammacoronavirus and Deltacoronavirus . The tree was reconstructed with sequences of the complete RNA- dependent RNA polymerase- coding region of the representative novel coronaviruses Shereen et al. (2020)"COVID-19 infection: origin, transmission, and characteristics of human coronaviruses." Journal of Advanced Research
  • 9. Phylogenetic Relationship of CoVs Based on the Whole Genome and RdRp Gene Nucleotide Sequences Pangolin-CoV, RaTG13, and SARS-CoV-2 were clustered into a well-supported group, here named the “SARS- CoV-2 group Zhang et al. (2019). Probable Pangolin Origin of 2019-nCoV Associated with Outbreak of COVID-19. Current Biology
  • 10. Comparison of complete genome organization similarity among SARS-CoV-2, Pangolin-CoV (91.02 %), and BatCoV RaTG13 (93.7 %). Considering the wide spread of SARSr-CoVs in natural reservoirs, such as bats, camels, and pangolins, these findings would be meaningful for finding novel intermediate SARS-CoV-2 hosts to block interspecies transmission. Zhang et al. (2019). Probable Pangolin Origin of 2019-nCoV Associated with Outbreak of COVID-19. Current Biology
  • 11. Amino acid sequence alignment of S1 protein and its phylogeny S1 protein of Pangolin-CoV is more closely related to that of 2019-CoV than to that of RaTG13. Within the RBD, we further found that Pangolin-CoV and SARS-CoV-2 were highly conserved, with only one amino acid change (500H/500Q) Zhang et al. (2019). Probable Pangolin Origin of 2019-nCoV Associated with Outbreak of COVID-19. Current Biology Tracing the transmissibility and pathogenicity determinant
  • 12. The S1/S2 cleavage site in the S protein is also an important determinant of the transmissibility and pathogenicity of SARS- CoV/SARS-CoV viruses. Four amino acid insertions (SPRRs) unique to SARS-CoV-2 SARS-CoV-2 S protein contains putative furin recognition motif (PRRARSV) similar to that of MERS-CoV, which has a PRSVRSV motif. The furin sequence motif at the S1/S2 site is missing in the S protein of Pangolin-CoV and all other SARS/SARSr-CoVs Zhang et al. (2019). Probable Pangolin Origin of 2019-nCoV Associated with Outbreak of COVID-19. Current Biology S proteinHost cell proteases cleave at S1/S2 cleavage site N-terminal S1 ectodomain C-terminal S2 membrane anchored protein (Recognize cell surface receptor) (drives fusion of viral envelope with cell membrane) This difference indicates the SARS-CoV-2 might gain a distinct mechanism to promote its entry into host cells
  • 13. Key research questions ??  why there are so many genetically divergent CoVs in bats? (Linked to the diversity of bat species)  What is the pathogenesis of most bat CoVs in humans? (Bottleneck: Isolation and identification of viruses from bats that pose a threat to humans apart from those viruses that were identified during the outbreaks)  What is the mechanism of disease transmittance? (For e.g. SARS CoV & SADS CoV were transmitted from bats to humans or swine; there exact transmission routes are unknown)  Bats as a natural reservoir of corona viruses (CoV), how can bats maintain CoVs long-term without showing clinical symptoms of diseases? Fan et al. (2019) Bat Coronaviruses in China, viruses