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Dr. Ali Nouri

@AliNouriPhD

1 Aug

@Nature

1/How SARS-COV-2 infects cells: ~24-40 Spike proteins stick out of the surface of the virus. They're key to the virus attaching itself to human cells. SARS-CoV-2 spikes are flexible & flop around, making it easier for multiple Spikes to grab cells. @Nature piece by @Scudellari 🧵

2/ The variants of concern have mutations in the S1 subunit of Spike protein, which includes RBD — the part of Spike that grabs the human ACE2 receptor. The Delta variant has multiple mutations in the S1 subunit, including some in RBD that may improve its ability to bind ACE2.

3/Once the S1 part of Spike binds human ACE2 receptor, another enzyne on human cells, TMPRSS2, cuts Spike’s S2 subunit and allows the virus to "fuse" with the human cell. The virus then "ejects its genome directly into the cell"

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Dr. Ali Nouri

@AliNouriPhD

20 Feb

📌CDC Report: Confirmed reinfection w/variant containing E484K mutation that's been associated with escape from several neutralizing antibodies. 45-year-old w/ no underlying conditions reinfected, 2nd episode more severe, higher viral load, though didn't require hospitalization🧵

@jbloom_lab

Viruses from both episodes were sequenced to confirm reinfection w/ distinct variant, as opposed to a single prolonged infection. The 2nd episode contained the E484K which @jbloom_lab has shown to be less susceptible to some antibodies 2/3

https://twitter.com/AliNouriPhD/status/1346482201119125505?s=20

Infections were 5 months apart. Unclear if immunity against 1st infection waned, or if variant evaded the immune response. But this highlights need for genomic surveillance to track variants w/possible implications for public health/immunization strategies
wwwnc.cdc.gov/eid/article/27…

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Dr. Ali Nouri

@AliNouriPhD

16 Jan

@UniversalMaski2

📌1/Infectious #SARSCoV2 in the air of a car 2 hrs after unmasked driver w/mild #COVID exited vehicle. Researchers found the virus in tiny air samples (0.25-0.5 um) and showed the virus retained ability to infect cells in a lab. H/T @UniversalMaski2 1/8🧵
rb.gy/odlbap

2/In July study found the virus to be stable in air. Mechanically generated aerosols/airborne #SARSCoV2 retained ability to infect cells for at least 16 hrs. Hardier in aerosols than SARS-1 or MERS. Helps explain why #airborne route is a major culprit: rb.gy/jxh0oh 2/8

3/#Airborne transmission has been observed in a restaurant from 20 ft away. How do they know? Video footage showed patient had no direct contact w/those who were infected far away. The restaurant lacked windows & ventilation system: rb.gy/5lh973 3/8

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Dr. Ali Nouri

@AliNouriPhD

7 Jan

1/📌Concerning case of reinfection: healthy 45 year old was reinfected with the genetically distinct SARS-CoV-2 variant that harbors the E484K mutation - this is the variant that was recently reported to escape neutralizing antibodies 1/6🧵

2/Second infection was more severe. Given the infections were 5 months apart its hard to know whether the immune response against the 1st infection simply waned, or, alternatively, if the variant virus managed to evade the immune response 2/6
preprints.org/manuscript/202…

3/Mutation is in RBD region of virus - the part that grabs human cell surface receptor, ACE2. Antibodies that bind RBD can block virus from entering our cells. But an earlier report this week showed that the E484K mutation in RBD is reducing the ability of antibodies to bind. 3/6

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Dr. Ali Nouri

@AliNouriPhD

5 Jan

1/📌BREAKING on #SARS_CoV_2 variants: the emerging variants in South Africa and Brazil that harbor the E484K mutation have "greatly reduced susceptibility" to neutralization by polyclonal serum antibodies derived from some individuals. This may have consequences for vaccines🧵

2/The "Receptor Binding Domain" on the Spike protein of the virus is a critical site for antibodies to bind to because those antibodies can block the virus from binding the ACE2 receptor on our cells. Mutations at that site are allowing the virus to escape antibodies.

3/Report shows neutralizing activity of convalescent sera (rich in polyclonal antibodies) was reduced >10-fold because of single mutation in RBD domain. They also found some sera samples that still neutralized, perhaps through antibodies binding other critical regions of spike.

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Dr. Ali Nouri

@AliNouriPhD

30 Dec 20

1/The #oxfordvaccine just approved in the UK is a version of an adenovirus (common cold virus) that instructs our cells to make the Spike protein of coronavirus. This trains our immune system so when we encounter #SARSCoV2, we can mount a defense. Here's how the vaccine works🧵

2/#SARSCoV2 is covered w/Spike proteins that help the virus grab human cells. To make the vaccine, researchers first isolated the gene that is responsible for making the Spike protein. They 'snipped' it from the rest of the genetic material of the coronavirus.

3/They then needed a delivery vehicle to get the Spike gene into our cells. So they took an adenovirus that normally infects chimpanzees, and genetically altered it so it can no longer replicate or cause disease. They then added the Spike gene to the adenovirus vector.

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