EID covid lecture
Influenza is ______ sense
negative
does chloroquine inhibit infection of human lung cells with SARS-CoV-2
no
so, if the majority of Americans were naturally infected in the 3rd and 4th waves of this pandemic, we may have enough protection to get us through Winter. Reinfections will eventually get more and more common, though. And we have no idea who's protected and who's not.
okay gary
vectors
organisms that spread disease from one host to another
what virus has specific trophism
papillomavirus only infects epithelial tissues
SARS-CoV-2 is a ______ sense single stranded RNA virus
positive
Negative sense viral RNA is complementary to mRNA and so must be transcribed to?
positive sense before translation
Is the corona positive or negative sense?
positive sense single-stranded RNA genome
Positive sense viral RNA can be translated immediately into _____.
proteins
_____ determine the viral tropism
receptors
(SARS-CoV-2) preferentially infects cells in the:
respiratory tract, but its direct affinity for organs other than the lungs remains poorly defined
SARS-CoV-2 stands for?
severe acute respiratory syndrome coronavirus 2 the strain of coronavirus that causes coronavirus disease 2019 (COVID-19)
reservoir
site or natural environmental location in which pathogen is normally found sometimes functions as source of pathogen
Animal viruses bind:
specific receptor proteins on their host cell
If Pangolins (or whatever) carry SARS CoV-2 or similar coronaviruses, we could have
spillover events over and over
Corona has enveloped viruses?
yes
SARS-CoV-2 is believed to have _____ origins.
zoonotic, it has close genetic similarity to bat coronaviruses
The S1 subunit of the spike protein binds to?
the ACE-2 enzyme on the cell membrane surface.
Tropism
the ability to infect a particular tissue type
The CDC says the reservoir of an infectious agent is?
the habitat in which the agent normally lives, grows, and multiplies. Reservoirs include humans, animals, and the environment. The reservoir may or may not be the source from which an agent is transferred to a host. For example, the reservoir of Clostridium botulinum is soil, but the source of most botulism infections is improperly canned food containing C. botulinum spores."
SARS-CoV-2 has affinity to?
the receptor angiotensin converting enzyme 2 (ACE2) on human cells (even more affinity than SARS does) and uses them as a mechanism of cell entry
period of infectivity
time during which source is infectious or is disseminating the organism
Transmission of zoonosis to human can be direct or indirect (T/F)
true
we speculate that organotropism influences the course of Covid-19 disease and, possibly, aggravates preexisting conditions" (T/F)
true
Cathepsin L requires an _______ environment to?
acidic environment to function and allow the virus to infect the cell, while TMPRSS2 does not.
A host transmembrane serine protease TMPRSS2 then does what?
activates the spike and cleaves ACE-2
The spike protein is responsible for?
allowing the virus to attach to and fuse with the membrane of a host cell this spike basically determines the host range
neither HCQ nor CQ can block the SARS-CoV-2 from infecting the lungs or stop the virus from replicating, why?
because this enzyme is not controlled by acidity
findings clearly show that that HQC can do what?
block the coronavirus from infecting kidney cells from the African green monkey. But it does not inhibit the virus in human lung cells
Internalized virions undergo ______, where genome is released from its capsid
uncoating
Human lung cells have very low levels of _____ ____ enzyme.
cathepsin L
kidney cells, need an enzyme called
cathepsin L for the virus to successfully infect them
A virus that has a genome that is more than 99% similar to SARS-CoV-2 has recently been isolated from pangolins - NOT SURE THIS IS CORRECT - my research shows a virus with 92% similarity from pangolins I can't find a paper stating 99% (it's yet to be published) so... who knows
cool gary
In green monkey kidney cells, both hydroxychloroquine and chloroquine _______ the acidity, which then?
decrease the acidity, which then disables the cathepsin L enzyme, and the virus is blocked from infecting the monkey cells
What virus has broad tropism
ebola, infecting many kinds of host tissues
The virus enters the cell in an ______?
endosome
The S, E, and M proteins do what?
hold together the viral envelope
Zoonose or zoonosis
is any infectious disease that can be transmitted from non-human animals to humans or from humans to non-human animals
MERS coronavirus reservoir
is believed to be camels and bats
SARS-CoV-2 reservoir
is not yet certain However, recent evidence suggests that both bats and the pangolin may be the reservoir.
Viral ssRNA can be positive or negative sense?
it can be either
SARS reservoir
likely of animal origin SARS coronavirus reservoir is believed to be civets and bats
Source?
location from which pathogen is transmitted to host
SARS-CoV-2 can be detected in multiple organs, including the
lungs, pharynx, heart, liver, brain, and kidneys
This study was done in vitro in Vero E6 cells. These are kidney cells. NOT lung cells.
...
RNA depended RNA polymerase is prone to?
making mistakes due to the no proofreading function. This causes many more mutations
COVID causes disease in?
mammals and birds, in humans and birds.
Most animal viruses enter host as?
virions (unlike bacteriophage which typically just send in genomic material)
Why do we have waves?
we dont know. we hypothesize it's largely driven by the combination of four factors
2005 paper:
Chloroquine is a potent inhibitor of SARS coronavirus infection and spread
Social media insert?
FAUCI is hiding the fact that hydroxychloroquine has been PROVEN to work against SARS-CoV-2
One of the hypothesis for waves being:
Human behavior: Once numbers start increasing, people start changing behavior (whether they know it or not). Even modest restrictions can bring numbers back down, like masking or cancelling plans. People did take the Delta wave seriously. The Kaiser Family Foundation reported an uptick in vaccinations due to Delta, hospitals filling up, and knowing someone who got seriously ill or died due to Delta. Human behavior plays a big role in wave patterns.
What happens inside the cell?
Inside the cell the virus is released from endosomes by acidification or the action of an intracellular cysteine protease, cathepsin
What is sense important?
It needs an RNA dependent RNA polymerase to convert negative sense RNA to positive
4th hypothesis for waves
Levels of Vaccine and/or Natural Immunity. As more people become immune, spread slows and the virus eventually stops because it runs out of people to infect. We, no doubt, saw this with vaccine rates and Delta. Highly vaccinated states, like Vermont (70% population fully vaccinated), came out relatively unscathed. As far as natural immunity, we saw this in Michigan. Michigan was hit hard with Alpha in April, which likely provided some protection against Delta. But Michigan numbers are starting to increase now, so we need to keep an eye on this.
Is this the last wave?
No one really knows, but it could be. At this point it's certainly partially (if not fully) dependent on the durability of natural immunity.
What is the makeup of the cell?
Nucleocapsid of helical symmetry. Large genome size - 26 to 32 kilobases Have a "corona" of club-shaped spikes that project from their surface, which looks like the solar corona
5th hypothesis of waves
Other factors: And there are likely many other reasons that play a less dominant role, like testing patterns (antigen becoming more dominant; less testing due to pandemic fatigue) and humidity. Others??
Coronavirus is ___ virus.
RNA
The N protein holds the?
RNA genome
What are the 4 structural proteins of SARS-CoV-2?
S (spike) E (envelope) M (membrane) N (nucleocapsid) proteins
Although these three novel coronaviruses are all quite distinct from each other, emerging evidence suggests that SARS-CoV-2 likely evolved from a virus related to the:
SARS coronavirus.
3rd hypothesis for waves
Seasonality. During non-pandemic times, most coronaviruses are seasonal. Other viruses, like the flu, are seasonal because of climate patterns (and human behavior). It's not a coincidence that our largest COVID19 wave was during the Winter months. But, again, this doesn't fully explain all waves, as we had some during the summer months too.
2nd hypothesis of waves
Social networks: This plays some sort of role too (and I think the most interesting). As people see their regular contacts and these networks reassert themselves, Delta runs out of places to go. This is highly dependent on how and where people mix. As we all know, schools just started, which would open social networks (not limit them). So this may only play a limited role with Delta.
The virus used the enzyme ______ to enter lung cells
TMPRSS2
lung cells need an enzyme called
TMPRSS2 (on the cell surface) for the virus to infect them
TMPRSS2 also acts on the? doing what?
TMPRSS2 also acts on the S2 subunit, facilitating fusion of the virus to the cell membrane
What is the step by step process of corona entering the cell
The coronavirus approaches the cell membrane An S1 subunit (red) at the end of a glycoprotein spike binds to a membrane-bound molecule of ACE-2 (blue) As more S1 subunits of the glycoprotein spikes bind to membrane-bound molecules of ACE-2, the membrane starts to form an envelope around the virus (an endosome) The process continues ... ... until the endosome is complete The virus enters the cell
In humans and birds:
mild to severe respiratory disease, common cold, SARS, MERS, COVID-19