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