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Covid 19 for Lecture final
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1-14 https://www.cdc.gov/coronavirus/2019-ncov/hcp/therapeutic-options.html 15-28 https://www.cdc.gov/mmwr/volumes/69/wr/mm6915e3.htm?s_cid=mm6915e3_w 29-52 https://www.nytimes.com/interactive/2020/04/03/science/coronavirus-genome-bad-news-wrapped-in-protein.html
Terms in this set (52)
To date, how many drugs or other therapeutics have been approved by the US Food and Drug Administration to prevent or treat COVID-19?
No drugs have been approved
What is remdesivir? What it's mode of action?
remdesivir is a broad spectrum antiviral medication
originally for Hep C
works by interferes with the action of RNA polymerase decreasing RNA production
Click on the Clinical Trials ( https://clinicaltrials.gov/ ) hyperlink and type in "remdesivir" into the "all studies" trial search in the "other terms" box. How many current trials for remdesivir are listed there? Which states and countries are involved in these clinical trials?
25 studies
china, uganda, france, california, canada, Norway, congo, Massachusetts, brazil
What are chloroquine and hydroxychloroquine? How many clinical trials are studying these drugs? (use the same search process listed for #3 above)
chloroquine treats malaria and works by inhibiting nucleosides and mitosis
266 studies all over the world
hydroxychloroquine works by blocking toll like receptors
88 studies on COVID
Which protozoan infection has hydroxychloroquine been used for in the past? Which specific, chronic inflammatory diseases are these drugs also used for (click on the Emergency Use Authorization and read the letter)?
malaria(plasmodium)
rheumatoid arthritis
lupus
What are some of the most dangerous side effects associated with hydroxychloroquine besides decreased immune function? (Go to RxList and search for "hydroxychloroquine" tablets side effects)
headache, dizziness, nausea, vomiting, stomach pain, hair loss, irritablility
What is convalescent plasma? (Go to the FDA website for Investigational COVID 19 Convalescent Plasma Recommendations). Has convalescent plasma been approved by the FDA for general use in treating COVID-19 in the United States?
no nots approved by FDA
What are some of the prerequisites for patient eligibility for the emergency individual authorization to receive convalescent plasma?
confirmed COVID test, shortness of breath, respiratory frequency, blood oxygen saturation, partial pressure of oxygen, lung infiltrates, respiratory failure, septic shock, multiple orang dysfunction or failure
What are some of the requirements for donor eligibility and qualifications for emergency individual authorization to donate convalescent plasma?
28 days covid free, neutralizing antibodies (IgG), meet typical blood donating requirements
Read the Aljazeera summary update on the search for a COVID vaccine here: "Where Does the World Stand on a Corona Virus Vaccine?" According to the April 2020 article, how many experimental vaccines are in the clinical testing stage (in humans)? How many are in pre-clinical (preliminary) trials?
three in testing take
67 in preclinical trials
What are the three phases of a typical clinical trial? Include the number of patients in each and typical time frame for completion (for phases 2 and 3).
1. small scale (100 ppl) to see if its safe
2. sever 100s to evaluate efficacy of vaccine
3. 100s of people to further assess the efficacy of the vaccine over a period of time
How long did Mike Ryan, head of the WHO Health Emergencies Program, estimate it would be before a COVID 19 vaccine was available?
at least a year away
Watch the 3 minute video imbedded in the article on the "Global Race to Find a Coronavirus Vaccine". What is the intended purpose of the experimental inhaler shown in the video?
The experimental inhaler is supposed to help restore interferon Beta that will help fight the virus
Look at the WHO's list of vaccine candidates posted here: "COVID-19 Candidate Vaccines". Under the "Platform" column, you can see the many different types of experimental vaccines being tested. Some of these vaccine types were covered in Tortora, chapter 18. What are the eight different platforms listed in this table?
live, killed, subunit (protein), DNA, RNA, Viral vector (replicating and non replication Adenovirus), Virus like particle (VLP)
What is COVID-NET?
the COVID 19 associated hospitalization surveillance network
How long was the study?
28 or 30 days
How many hospitalized patients were included in the study? What hospitalization rate does this represent per 100,000 population?
1,482
4.6 per 100,000
How many states were included the study?
14 states
What percentage of the US population does the study cover?
10%
What were the age groupings in the study?
0-4, 5-17
What % of the studied patients were male? Is this representative of the % of males in the general population?
54.4% male
49% residents are male
Which racial group was disproportionately affected by the virus in this study?
45% white
33% black
8% hispanic
What were the 5 most common underlying health conditions seen in approximately 90% of the hospitalized patients? List the underlying condition and the % seen in this study for each.
What were the 5 most common underlying health conditions seen in approximately 90% of the hospitalized patients? List the underlying condition and the % seen in this study for each.
What was the median interval of time between symptom onset and hospitalization?
7 days
What were the 4 most common signs and symptoms at admission to the hospital?
cough 86.1%
fever or chills 85% shortness of breath 80%
gastrointestinal- 26.7% diarrhea 24.4% nausea or vomiting
What percent of the hospitalized patients were at least 50 years of age?
74%
What were the three important limitations to the study, according to the authors?
1. hospitalization by age might change as additional cases are identified
2. minimum case data to produce weekly age- stratified hospital rates are usually ready within 7 days
3. testing for ears among patrons is preformed at the discretion of treating health care providers and testing practices and capabilities might cary across providers and facilities
Which important preventative measures did the authors emphasize to protect older adults and those with underlying medical conditions?
ocial distancing, respiratory hygiene, and wearing face coverings in public settings where social distancing measures are difficult to maintain
What was the source of the virus whose genetic information was sequenced and studied in this article?
41 year old man who worked at the seafood market in wuhan
What type of genetic information does the COVID-19 virus have? RNA or DNA? ds or ss? + or -? (see lecture notes)
RNA, SS
Approximately how many genes does the novel Corona virus have?
29 genes
Approximately how many total nucleotides in the genome?
less than 30k
What is the ORF1ab (=Open Reading Frame 1ab)? How many non-structural proteins does it contain?
the first viral protein, open frame, long piece of messenger RNA is made
16 proteins
What is the function of NSP1 (=Non-Structural Protein 1)?
slows down the infected cell's production of its own proteins to make more virus proteins
What is the function of NSP3?
cutting loose other viral proteins and alters many infected cells proteins
What is the function of NSP4?
helps build fluid filled bubbles within infected cells, inside the bubbles new copies of the virus are constructed
What is the function of NSP5?
cuts, freeing other NSP proteins to carry out their own jobs
What is the function of NSP9?
infiltrates channels in cells nucleus and influences movement of molecules in and out of the nucleus
What is the function of NSP10 and NSP16?
camouflage the virus's genes so that they dont get attacked
What is the function of NSP12? How does it relate to the antiviral drug remdesivir?
assembles genetic letters into new virus genomes
Remdesivir interferes with NSP12
What is the function of NSP13?
unwinds RNA so that other proteins can read its sequence and make new copies
What is the function of NSP14?
cuts out error added by NSP12 so that the correct letter can be added instead
What is the S protein? How does it interact with the ACE-2 receptor in human tissues?
forms the outer layer of covid and protects the RNA inside
spike from S protein extend and attach to a protein and invades the cell in the airway
What is the significance of the 12 letter insertion mutation found within the gene for the S protein in COVID-19?
helps the spikes bind tightly to human cells to evolve from a virus that was from bats to humans
What is the function of ORF3a?
poles a hole in the membrane of an infected cell, making it easier for a new virus to escape
triggers inflammation
What is the E protein?
envelope protein, forms the oily bubble of the virus
latches onto proteins that help turn our own genes off and on
What is the function of ORF6?
Brocks signals that infected cell would send out to the immune system
locks some of the cells own virus fighting proteins, the same ones targeted by other viruses such as polio and influenza
What is the function of ORF7a?
cuts down an infected cells supply of tetherin(cells ability to snare a virus)allowing more of the ruses to escape
What is the function of ORF9b?
blocks interferon, a key molecule in the defense against viruses
What is the N protein?
protect the risks RNA, keeping it stable inside the virus
Free response: How could knowing the sequence of nucleotides and types of proteins expressed in COVID-19 help scientists in the search for effective treatments and possible vaccine targets? Give a specific example for a possible drug treatment strategy and potential vaccine target.
Knowing the sequence of nucleotides expressed in COVID-19 is very important to search for effective treatment because you can pick a certain sequence and remove that particular sequence that may cause a mutation that is linked to COVID-19 illness. Examples of treatments may include amantadines and saquinavirs that will interfere with uncoating and assembly but also nucleoside analog drugs that are antiviral and currently protect against shingles, herpes, hepatitis and HIV. A potential vaccine would target the attachment of the virus and could contain an inactivated virus, such as the flu vaccine. A vaccine that contains inactivated viruses help the production of antibodies to protect from infection.
What is the M protein?
forms outer coat of the virus
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