COVID-19 antivirals and vaccines (Megathread)

[John Cuthber]

13 hours ago, Enthalpy said:

It's the one chemical that kills most people in household accidents.

I'm willing to bet that water and alcohol each kill more. Both are vital in the fight against Covid

But the point isn't "what kills most people?", its what "saves more people than it kills" to the greatest extent?

 

If people have bleach, but not peroxide then telling them not to use bleach is a serious mistake.

[Strange]

On 3/18/2020 at 8:27 PM, Enthalpy said:

it tells that Covid-19 "lives" shorter on a surface of copper than of stainless steel, cardboard or polymer. Silver was not tested.

Looking at the large package the delivery guy just dropped off and wonder "what about cardboard?"

[PhilGeis]

Please think critically.  Read the paper - not just the comments.  Cardboard  was tested and wasn't much worse than copper.

Edited March 20, 2020 by PhilGeis

[Strange]

18 minutes ago, PhilGeis said:

Please think critically.  Read the paper - not just the comments.  Cardboard  was tested and wasn't much worse than copper.

Thanks. I didn't think they would test cardboard (I assumed it was with respect to work surfaces and similar things)

[hypervalent_iodine]

!

Moderator Note

I have merged a number of threads and posts into this one to decrease the clutter. 

 

[stangerzv]

Latest Updated (Added, prospect of Carica Papaya Leaf as Interleukin IL-6 Inhibitor)

Papaya leaves extract; a possible weapon against Covid-19

 

M.S. Shukor1 and M.Y. Shukor2

 

1Snoc International Sdn Bhd, Lot 343, Jalan 7/16 Kawasan Perindustrian Nilai 7, Inland Port, 71800,  Negeri Sembilan, Malaysia.

2Department of Biochemistry, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, UPM 43400 Serdang, Selangor, Malaysia.

Covid-19 is now a pandemic affecting humans at a global scale. Researchers are still trying to find a cure and the vaccine to fight this disease. Drug-based cure and vaccine are overwhelmingly virus-specific and newer drugs and vaccines are needed to resist new novel viral infections. A shift towards herbal remedies to fight viral infections is an approach that can be explored especially in poorer countries or when drugs and vaccines are still not available. One of the top herbal remedies that emerges as a prime weapon for viral infection is Carica papaya, where the leaves extract has been tested in clinical environment in patients infected by the dengue virus. In two studies, platelets, white blood cells and neutrophils counts were back to normal after the administration of papaya leaves aqueous extract and the infected patients recovered (Ahmad et al. 2011; Kumar et al. 2015). Further research has demonstrated that papaya leaf extract decrease dengue complication through another route by inhibiting viral production. A study suggests that papaya leaves extract significantly cause the expression of NS1 and envelope proteins to be lowered in DENV-infected THP-1 cells. A significant lowering of the intracellular viral load supports papaya leaves extract antiviral activity (Sharma et al. 2019). In addition, papaya extracts and papaya-associated phytochemicals possibly enhance recovery in dengue infected patients through their anti-inflammatory and immunomodulatory properties (Pandey et al. 2016). A study shows that nine selected ligands from Carica papaya leaves show good binding to viral proteins from dengue, influenza A (H1N9) and chikungunya (Narayanaswamy et al. 2017).

As more and more wonderful properties of papaya leaves extract are reported in the literature, researchers began to use the extracted phytochemicals from the plant to combat other viral infections either in vivo, in vitro or in silico. SARS-CoV-2 is the novel virus that causes Covid-19. It has not benefit from the usage of papaya extract to fight its infection, not yet, but there is a growing body of evidences that suggest its probable usage to combat Covid-19. For a start, the anti-inflammatory and immunomodulatory properties of papaya leaves extract can increase an infected person chance of recovering from the infection. The papaya leaves extract is able to reduce the severity of cytokine storm in dengue infection in mice model (Norahmad et al. 2019). Cytokine storm is one of the most important mechanisms that lead to deaths of Covid-19-infected patients (Chen et al. 2020). Cytokine storm occurs when the lungs of infected patients become severely inflamed due to the massive overproduction of a host of mediators such as interleukins, interferons, tumour necrosis factor, macrophage and other factors which are lumped together as cytokines or chemokines. Cytokine storms often lead to infected cells dying through apoptosis and necrosis leading to severe tissue damage and haemorrhages triggering multiple organ failure (Tetro 2020; Chen et al. 2020; Yao et al. 2020). The inflammation of the lungs in the Covid 19 patient is due to the Interleukin IL-6, Sanofi and Regeneron is running a Clinical trial named Kevzara a fully-human monoclonal antibody to block the Interleukin IL-6 receptors. (Sanofil and Regeneron). Clinical trial on the carica papaya leaf extract (CPLE) on the dengue fever found a decrease of 18% on the Interleukin IL-6 of the treated patients with (CPLE) and an increase of 13% in the placebos subgroup (Dipu T. Sathyapalan et al. 2020). This finding shows that CPLE could be used as an inhibitor candidate for the Interleukin IL-6 in reducing the Covid 19 Cytokine Storm.

In another study, patients having virus-induced lung damage were given fermented papaya preparation for one month. The researchers observed an increase in salivary IgA and increase in phase II and SOD enzyme expression levels, which are essential antioxidants in the respiratory tract (Marotta et al. 2012). Consumption of papain leaf extract can probably help in fighting Covid-19 infection, but more studies are needed to support this premise. An important step for a start is the in silico docking behavior of potential ligands from papaya leaves extract to the papain-like Covid-19 protease; one of the main targets of Covid-19 antiviral drug screening strategy (Arya et al. 2020; Zhang et al. 2020). 

 

Reference

 

Ahmad N, Fazal H, Ayaz M, Abbasi BH, Mohammad I, Fazal L (2011) Dengue fever treatment with Carica papaya leaves extracts. Asian Pacific Journal of Tropical Biomedicine 1, 330–333. doi:10.1016/S2221-1691(11)60055-5.

Arya R, Das A, Prashar V, Kumar M (2020) Potential inhibitors against papain-like protease of novel coronavirus (SARS-CoV-2) from FDA approved drugs. doi:10.26434/chemrxiv.11860011.v2.

Chen C, Zhang XR, Ju ZY, He WF (2020) [Advances in the research of cytokine storm mechanism induced by Corona Virus Disease 2019 and the corresponding immunotherapies]. Zhonghua Shao Shang Za Zhi = Zhonghua Shaoshang Zazhi = Chinese Journal of Burns 36, E005. doi:10.3760/cma.j.cn501120-20200224-00088.

Kumar DrCVMN, Vadlamudi T, Venkatamuni A, Vardhan V, Prasad Y, Ravi U, D.V.R. S (2015) Therapeutic potential of Carica papaya l. leaf extract in treatment of dengue patients. International Journal of Applied Biology and Pharmaceutical Technology 6, 93–98.

Marotta F, Naito Y, Jain S, Lorenzetti A, Soresi V, Kumari A, Carrera Bastos P, Tomella C, Yadav H (2012) Is there a potential application of a fermented nutraceutical in acute respiratory illnesses? An in-vivo placebo-controlled, cross-over clinical study in different age groups of healthy subjects. Journal of Biological Regulators and Homeostatic Agents 26, 285–294.

Narayanaswamy R, KW L, ME N (2017) Molecular docking analysis of Carica papaya Linn constituents as antiviral agent. International Food Research Journal 24, 1819–1825.

Norahmad NA, Mohd Abd Razak MR, Mohmad Misnan N, Md Jelas NH, Sastu UR, Muhammad A, Ho TCD, Jusoh B, Zolkifli NA, Thayan R, Mat Ripen A, Zainol M, Syed Mohamed AF (2019) Effect of freeze-dried Carica papaya leaf juice on inflammatory cytokines production during dengue virus infection in AG129 mice. BMC Complementary and Alternative Medicine 19,. doi:10.1186/s12906-019-2438-3.

Pandey S, Cabot PJ, Shaw PN, Hewavitharana AK (2016) Anti-inflammatory and immunomodulatory properties of Carica papaya. Journal of Immunotoxicology 13, 590–602. doi:10.3109/1547691X.2016.1149528.

Sanofi & Regeneron https://www.pharmaceutical-technology.com/news/sanofi-regeneron-kevzara-covid-19/

Sharma N, Mishra KP, Chanda S, Bhardwaj V, Tanwar H, Ganju L, Kumar B, Singh SB (2019) Evaluation of anti-dengue activity of Carica papaya aqueous leaf extract and its role in platelet augmentation. Archives of Virology 164, 1095–1110. doi:10.1007/s00705-019-04179-z.

Tetro JA (2020) Is COVID-19 receiving ADE from other coronaviruses? Microbes and Infection. doi:10.1016/j.micinf.2020.02.006.

Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, Liu X, Zhao L, Dong E, Song C, Zhan S, Lu R, Li H, Tan W, Liu D (2020) In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. doi:10.1093/cid/ciaa237.

Zhang D, Wu K, Zhang X, Deng S, Peng B (2020) In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus. Journal of Integrative Medicine 18, 152–158. doi:10.1016/j.joim.2020.02.005.

Efficacy & safety of Carica papaya leaf extract (CPLE) in severe thrombocytopenia (≤30,000/μl) in adult dengue – Results of a pilot study Dipu T. Sathyapalan et al 2020, plosone)

 

[Enthalpy]

The friend sent me pictures of copper tape on the doorhandle:

The sheet's edges are a weak point of the construction. They might hurt the user or accumulate dirt and viruses at the concave angles, spoiling the benefits of copper.

That reason favours the broad copper tape over my proposed helical winding of narrow tape.

Rounded corners would stay glued on the handle and be less dangerous.

Maybe solder would secure the edges and fill the concave angles. I'd also flatten the edges by pressing with a hard round tool, maybe a light hammer, before sticking and soldering, and sand after soldering.

It's not investigated against Covid, but usually silver sterilizes better than copper does. Solutions exist to deposit it on copper by immersion.

[13mh13]

Say I get a pathogen infection, my immune system fights it off, and now I'm immune. 

Now, I've got a bunch of dead and/or weak pathogen particles in me. 

Can I pass these dead/weak particles off as "immunization" to others NATURALLY ? These may be via std. pathology communication transport: sneeze, breath, touch/contact. Essentially,  this is analogous to medical immunization inoculation or vaccine nasal spray. 

How realistic is this scenario?

If realistic, how common is this situation in Nature?

Edited March 23, 2020 by 13mh13

[Endy0816]

Immune system may inactivate some via fever and eats any it finds, but you'll still have functional viruses floating around.

Using vaccines to prep the immune system is better really.

[Enthalpy]

One step better, IF silver destroys the Covid virus efficiently:

Deposit a silver film directly on the handle or the item. Solutions exist for that. The surface acts as a catalyst, and it doesn't have to be metallic. Easier than copper, mechanically safer.

Primers or treatments may be useful, or not, to let the silver layer adhere on varied materials. Handles are often coated with some unreactive polymer. Degreasing is a minimum, maybe sanding a little bit with quite fine paper.

Silver handles could be useful in hospitals for instance.

Marc Schaefer, aka Enthalpy

[13mh13]

3 hours ago, Endy0816 said:

Using vaccines to prep the immune system is better really.

My query was not about "Using vaccines to prep the immune system" . By "vaccines " , I assume you mean  synthetic vaccines (shots!). 

If humans only recently discovered immunization via shots and nasal sprays, then Nature might use similar strategy  . At least via physical contact, body fluid exchange,  snot, etc. See my orig. query.

[CharonY]

The immune system does not only inactivate pathongens and then let's them float around. They basically take them apart. There is no transmission beyond that point.

[Bradley Young]

I know Im a small fish in a big pond, but I just want to help.  This is a recent convo with my professor and I'd like to know what are your thoughts.

 

 

ME:  I have been doing some  digging on a couple of ideas that I had. I was wondering if there were a way to distrupt the (Van der Waal forces) of the lipid bilayer of the virus inside of the body the same way polarized soap molecules do outside of it. Just a civil scientist thought. Orrrrr some way for the lysosomes to become hypersensitive to the invader... Thoughts...
PROF FLETCHER:   Counterpoint: what else in the body has a lipid bilayer? what would be the danger in a pharmaceutical that emulsified lipids?

 
ME:  Yeah, I thought about that too and wondered if there were a way to specialize it only to the virus. Slippery little devils. lol.
 How about increasing the signal sensitivity of the lysosomes to interrupt the infectious cycle within the cell.
I was also curious about affecting the cell's receptors rendering it non-susceptable or permissive.  Particularly cytokine and/or glycoprotein sensitivity.  Or differentiating viral lipids over cellular as the desired target.
Wish I had a magic wand. 

PROF FLETCHER:FHey Bradley,  I'm glad you're putting critical thought into this issue!  Hand soap works by emulsifying lipid molecules.  While it is true that disrupting the  Van der Waals forces that are holding together the bilayer surrounding the virus, it's important to consider what else in the body has that similar structure and what else may be affected by this disruption.  So my question is this: where else have we seen this bilayer structure? what else might be affected by disrupting lipid molecules? how would you increase specificity to differentiate between viral and human cell membrane?

Yes, increasing sensitivity is also a good line of thinking.  Do you have any thoughts on what might need to happen to make the lysosomes more sensitive?

ME:  Thank you for all of your wisdom and great feedback. I truly appreciate it😊
   These are great leads that I do intend to follow-up on. Thanks🤓

This is a later convo with a medical biotechnologist:

Vishnu: You could use the natural pH changes occurring in the virus-infected cell to trigger a drug release. A salient feature is the reduction in intracellular pH (pHi) of virus-infected cells.

If I'm not mistaken, lysosomal enzymes are acid hydrolases, which are active at the acidic pH5. They are not active at the neutral pH (about 7.2). 

Degradable, pH-sensitive, membrane-destabilizing, comb-like polymers have been used previously for nucleic acids delivery into a cell. It is not implausible to think of using such a pH-sensitive extra sac around the lysosomal complex to deliver it into a virus-infected cell. This sac will automatically enter a low pH cell. It will disintegrate once inside a virus-infected cell exposing the lysosomal enzymes. 

I'm not a biomaterials trained person so, I can't actually name many polymers, but there are biomaterials and nanomaterials capable of doing this.  One example is pH-sensitive ethylacrylic acid (EAA) monomers and hydrophobic hexyl methacrylate monomers (HMA).

ME: So you are saying introducing it through phagocytosis like a Trojan horse. I didn't even think of pH affecting lysosomal enzymatic activity.


Vishnu:  Yes, introduce it like phagocytosis. Yup, pH affects a lot of things. It is a decent hypothesis to test. I'm pretty sure there will be some specificity issues. Maybe there is a gradient of pH around the virus-infected cell. It may dampen the specificity. I don't know. 

Awesome you're digging deep into this. 🙂 👍🏽 
You too! Namaste and Merci! 

Edited March 23, 2020 by Bradley Young

[swansont]

On 3/20/2020 at 11:04 AM, PhilGeis said:

Please think critically.  Read the paper - not just the comments.  Cardboard  was tested and wasn't much worse than copper.

"up to 4 hours on copper, up to 24 hours on cardboard"

A factor of 6 is significant, wouldn't you say?

4 hours ago, Enthalpy said:

 Silver handles could be useful in hospitals for instance.

Brass is already a standard material for doorknobs and push plates.

Unfortunately, so are plastic and stainless steel, which are often chosen for aesthetic reasons (they don't tend to tarnish)

[CharonY]

2 hours ago, swansont said:

"up to 4 hours on copper, up to 24 hours on cardboard"

A factor of 6 is significant, wouldn't you say?

If you look at the images, it appears that there is a different limit of detection for copper than for all the other substrates (about an order of magnitude). So to me it is not immediately clear whether viability is actually that different. After 4 hours there is only a slightly lower absolute titer than on cardboard. 

There is a rapid drop even at T0 on cardboard (i.e. folks recover less immediately after deposition), which is probably due to adsorption into the fibers.

[PhilGeis]

CharonY is exactly right.  If you applied the same level of detection used for copper - to cardboard you'd see cardboard only moderately different.    Again swansont - read the paper.

[13mh13]

5 hours ago, CharonY said:

The immune system does not only inactivate pathongens and then let's them float around. They basically take them apart. There is no transmission beyond that point.

Have naturally-immunized (self-immunized) organisms ever been formally studied to asses, e.g., whether they are not spitting, sneezing or breathing out dead/weakened particles (e.g., viral remnants )?

 

[StringJunky]

8 minutes ago, 13mh13 said:

Have naturally-immunized (self-immunized) organisms ever been formally studied to asses, e.g., whether they are not spitting, sneezing or breathing out dead/weakened particles (e.g., viral remnants )?

 

The virus particles are effectively disassembled, as CharonY said, so how likely will there be any immunologically-recognizable remnants after that process?

[Endy0816]

6 hours ago, 13mh13 said:

My query was not about "Using vaccines to prep the immune system" . By "vaccines " , I assume you mean  synthetic vaccines (shots!). 

If humans only recently discovered immunization via shots and nasal sprays, then Nature might use similar strategy  . At least via physical contact, body fluid exchange,  snot, etc. See my orig. query.

Look into macrophages.

 

[swansont]

14 hours ago, CharonY said:

If you look at the images, it appears that there is a different limit of detection for copper than for all the other substrates (about an order of magnitude). So to me it is not immediately clear whether viability is actually that different. After 4 hours there is only a slightly lower absolute titer than on cardboard. 

There is a rapid drop even at T0 on cardboard (i.e. folks recover less immediately after deposition), which is probably due to adsorption into the fibers.

Absorption would make sense.

Adsorption is a surface effect.

[studiot]

The experts tell us that the reason why washing hands is so effective against CV is that the virus particle  is held together by a fatty blob.
washing with soap/detergent/surfactant attacks this blob and  so the virus falls apart.

Given this information I was wondering about the possibility of introducing a suitable surfactant into the lungs of seriously affected patients to reduce the concentration of virus and give their own defences a  better chance.

Pulmonary lavage is not common but has been done for other purposes.

https://respiratory-research.biomedcentral.com/articles/10.1186/1465-9921-6-138

[yunus shukor]

maybe doctors can try

https://en.wikipedia.org/wiki/Pulmonary_surfactant

Composition

• ~40% dipalmitoylphosphatidylcholine (DPPC);^[5]
• ~40% other phospholipids (PC);^[5]
• ~10% surfactant proteins (SP-A, SP-B, SP-C and SP-D);^[5]
• ~10% neutral lipids (Cholesterol);^[5]
• Traces of other substances.

tweaked it a bit in vitro to see the best composition or addition that can kill the virus

[Strange]

I'm quite sure that medical researchers with years of experience and expertise will be thrilled to see all these suggestions from random people on the internet. I bet they have been really struggling to come up with ideas.

[Enthalpy]

58 minutes ago, Strange said:

I'm quite sure that medical researchers with years of experience and expertise will be thrilled to see all these suggestions from random people on the internet. I bet they have been really struggling to come up with ideas.

Experts are seldom thrilled by suggestions made by outsiders, but outsiders bring most progress. Yes, ideas are badly scarce,. And on the Internet, you find the same people as in companies, with the same skills but not as grossly misused.

Think at the Steinway. The production of fullerenes or graphene. The chipcard. The contactless chipcard. Many solutions for the Fukushima disaster. Paypal. SpaceX. Tesla. And so on and so forth.

Waiting for experts, or worse for known experts, to solve everything and bring all innovation is a recipe for stagnation. It's also contrary to observation.

[Strange]

2 minutes ago, Enthalpy said:

outsiders, but outsiders bring most progress

Citation needed.

Quote

Think at the Steinway. 

The piano? Designed by a piano designer.

Quote

The production of fullerenes

Predicted by a computational chemist. First manufactured by a chemist.

Quote

or graphene

First theorised by a physicist. Further refined by other physicists and chemists. Manufactured by physicists and chemists.

Quote

chip card

Invented by two German engineers.

Quote

paypal

Started by software engineers and money men.

11 minutes ago, Enthalpy said:

Waiting for experts, or worse for known experts, to solve everything and bring all innovation is a recipe for stagnation. It's also contrary to observation.

All the advances you mention were made by experts in their field. (You might have been able to find a couple of examples from mathematics and astronomy; they are among the few areas where outsiders do occasionally make significant contributions.)

Not a single one was the result of some random person with no expertise in the subject making uninformed suggestions.

But this is just another off-topic hijack by the conspiracy minded. So we will leave it there.