In this lecture we’re gonna discuss the
replication cycle of coronavirus as well as emerging targets for pharmacological antiviral
interventions. So without further ado let’s get right into
it. The present outbreak of a coronavirus-associated
acute respiratory disease is the third documented spillover of an animal coronavirus to humans
resulting in a major epidemic. The Coronavirus Study Group of the International
Committee on Taxonomy of Viruses formally named the new coronavirus as “severe acute
respiratory syndrome coronavirus 2,” or SARS-CoV-2. Human-to-human transmission of SARS-CoV-2
occurs primarily via respiratory droplets from coughs and sneezes. Like other coronaviruses, SARS-CoV-2 has four
structural proteins, known as the “S” for spike, “E” for envelope, “M” for membrane, and “N” for nucleocapsid,
which encapsulate single-stranded viral RNA. Now, spike is the main protein that interacts
with the host cell receptors. In the first step of receptor binding, spike
protein is cleaved into S1 and S2 by the host cell protease, one of which is transmembrane
protease serine 2 abbreviated as TMPRSS2. The main function of S1 subunit is to bind
with the host cell surface receptors, while the function of S2 subunit is to mediate membrane
fusion. So one of the potential therapeutic approaches
is to either develop vaccine that contains antigens derived from the spike protein, which
can boost recognition of the virus by the immune cells or to develop monoclonal antibodies
that bind to the coronavirus spike protein and block the interaction with human cells. Another potential target is transmembrane
protease serine 2, which appears to be essential for entry and viral spread of the coronavirus. One agent that is currently being tested,
called Camostat Mesylate has shown to inhibit TMPRSS2 activity and thus is being considered
as a potential anticoronavirus candidate. Now, recent protein modeling studies on the
spike protein suggest that SARS-CoV-2 has a strong binding affinity to human angiotensin
converting enzyme 2 (ACE2) receptors and likely uses them as a mechanism for cell entry. One location where ACE2 receptors are highly
expressed is type II alveolar cells, which are found in the lungs. However ACE2 receptors are also found in many
extrapulmonary tissues including heart, kidney, endothelium, and intestine. So another potential drug targets could be
the interaction sites between ACE2 and spike protein. One compound that has already been found during
recent computational study, which is predicted to bind with the binding interface of the
Spike–ACE2 complex, is a natural flavonoid called Hesperidin. Now studies in mice demonstrated that coronavirus
binding of spike protein to ACE2, downregulates the receptor, and thereby contributes to severe
lung injury. This suggests that delivery of excessive soluble
form of ACE2 may competitively bind with SARS-CoV-2 and not only neutralize the virus but also
rescue cellular ACE2 which regulates the renin-angiotensin system to protect the lungs from injury. One small study has already found recombinant
human ACE2 to be safe, with no negative hemodynamic effects in healthy subjects. Now, moving on to the next replication step. So after uncoating, first the genomic RNA
of coronavirus acts as an mRNA for translation of the replicase polyprotein 1a (pp1a) and
1ab (pp1ab). Autoproteolytic cleavage of these polyproteins
then produces number of non-structural proteins including RNA-dependent RNA polymerase, helicase
and nonstructural protein 3, 4, and 6. These nonstructural proteins 3, 4, and 6 are
thought to be responsible for anchoring the coronavirus replication/transcription complex
through recruitment of intracellular endoplasmic reticulum membranes to form double membrane
vesicles abbreviated as DMV. RNA-dependent RNA polymerase (RdRp) and helicase
localize to double membrane vesicles and drive the production of subgenomic RNAs (sgRNAs)
from which the structural and accessory proteins are produced in the next phase of translation. Now RNA-dependent RNA polymerase (RdRp) is
a target of investigational drugs such as Remdesivir and Favipiravir. Preliminary research has shown that both of
these agents inhibit RNA-dependent RNA polymerase and thus might be useful in treatment of early
or mid-stages of the coronavirus disease. Allright, going back to the next replication
step, once synthesized, transmembrane structural proteins “S”, “M”, and “E” are inserted, and folded
in the endoplasmic reticulum (ER) and then transported to the Endoplasmic reticulum–Golgi intermediate
compartment abbreviated as ERGIC. The “N” proteins on the other hand bind the
viral genomic RNA in cytoplasm to form nucleocapsid. Once the final virion assembly occurs in the
intermediate compartment, mature virions are released via smooth-walled vesicles by exocytosis. Now, in addition to the investigational agents
that we discussed thus far, there are few antiviral drugs that are already on the market
that have been reported as potentially effective against coronavirus. One of them is antimalarial drug called Chloroquine,
which is thought to exert its antiviral activity in part by increasing the pH in host-cell
lysosomes, which in turn inhibits hydrolytic activity of protease enzymes that are required
for processing of viral glycoproteins during infection. Other drugs of interest are the combination
of Lopinavir and Ritonavir, as well as Darunavir and Cobicistat, which belong to class of drugs
known as protease inhibitors. These drugs were originally designed to block
HIV viral replication. However molecular docking studies have shown that they may also interact with some proteins that are required for replication of coronavirus. And with that I wanted to thank you for watching
I hope you enjoyed this video and as always stay tuned for more.

41 Replies to “Pharmacology – CORONAVIRUS (MADE EASY)”

  1. There are a few prevention measures of avoiding it to hijack our lungs :
    1) Vitamin D3, there published researches on how it prevents lung diseases and aids our respiration and not just for Calcium absorption.

    2) Turmeric activates Autophagy and inhibits NF-κβ pathways, so, it may help with us being stronger from our immune.

    3) Garam Masala, it has spices like Clove (which has Eugenol) , Fennel, Cumin (has thymol), chilly (Capsaicin) some of the very strong inhibitors of free radicals that binds free cells from surfacing so that the virus doesn't get to hijack the cells to infect them on the RNA replication.

    4) Use a strong soap that has high Alkaline values, BBC has a report which proves its efficacy over alcohol based sanitizers.

    5) Consume Cruciferous Vegetables since they activate the NRF2 pathways and help detox our bodies.

    6) Consume Nitrate rich foods that aid in dilation of vessels and oxygenate the cells.

    There's, a gift that Vegetables usher us with yet, we adopt a heavy Carnivore lifestyle.
    Of all major areas of Corona Virus transmissions, almost all of them are heavy meat consumers, have high protein and high carb diets. Not promoting a vegan agenda ,since I'm not an absolute vegan myself, my Vegetarian lifestyle has not only made me ageless, but my kidney function has jumped 40 points something my doctor is shocked to beleive, my cholesterol has gotten normal, I look 25 now and feel like 20 within,

    Be safe guys, whatever it is , try to consume Vegetables at large because they're full of Apigenin, Luteolin, Rutin, Quercetin, Kamperferol and so many nutrients that defend us.

  2. Just a friendly reminder: The content of this video is intended for informational and educational purposes only, and is not intended for medical advice. Please consult with your doctor or other health professional for case-specific recommendations.

  3. Thank you so much sir for uploading the video it is very helpful for B pharmacy students. Your videos are very helpful in my academic year thank you so much sir

  4. Is coronavirus about $ for Rx industry from the coming vaccine ? Wake up people & Stop acting like sheep. Find the book entitled: "NWO unleashes Agenda 21 The vaccine killed them all"

  5. Sir can you please make videos on drugs acting on uterus, endocrine,blod forming organs,git disease, respiratory system andnrenal pharmacology?plssss sir i have exam in June and i want to see more of your videos

  6. wash your hands…. eat healthy… DON'T WATCH TV don't listen radio if mention CORONA. / all that information nonsense. It just makes people exhausted/paranoid….. Stress affect our natural immunity SYSTEM. It makes you OWER THINK. Look how much €££€£$ world bank planning to lend.. PAY ATENTION into that loan amount and what conditions of their fundig ..

  7. Bottom line, everybody should go to the spice cabinet and wash down a pinch of oregano twice a day to block the spike protein. Oregano is superconcentrated in luteolin (one of the top ranked flavonoids, along with quercetin and their glucosides, in bonding to the spike protein).

  8. sir, if you can please do a focused thorough video on the drugs chloroquine and hydroxychloroquine as there as they are being hailed as miracle drugs already and much misinformation is spreading about it's mechanism of action.
    Thankyou for your work as always

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