Clinical management of severe acute respiratory infection (SARI) when COVID-19 disease is suspected *notes to self

CDC What to do if you are sick with
coronavirus disease 2019 (COVID-19)
If you are sick with COVID-19 or suspect you are infected with the virus that causes COVID-19, follow
the steps below to help prevent the disease from spreading to people in your home and community.

[link to www.cdc.gov (secure)]

Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods

[link to www.sciencedirect.com (secure)]


Table 1. Potential PLpro inhibitors from ZINC drug database (compounds in the table are ranked according to their docking scores).

No. Drug name Structure Pharmacological function
1 Ribavirin Image 2 Anti-virus
2 Valganciclovir Image 3 Anti-virus
3 β-Thymidine Image 4 Anti-virus
4 Aspartame Image 5 Non-carbohydrate sweetener
5 Oxprenolol Image 6 Anti-hypertensive, anti-angina,
anti-arrhythmic effects
6 Doxycycline Image 7 Anti-bacterial effect
7 Acetophenazine Image 8 Anti-psychotic effect
8 Iopromide Image 9 Low osmolar, non-ionic contrast agent
9 Riboflavin Image 10 Treatment of vitamin B2 deficiency
10 Reproterol Image 11 Treatment of bronchial asthma
11 2,2′-Cyclocytidine Image 12 Anti-tumor
12 Chloramphenicol Image 13 Anti-bacterial effect
13 Chlorphenesin carbamate Image 14 Muscle relaxant effect
14 Levodropropizine Image 15 Anti-tussive effect
15 Cefamandole Image 16 Anti-bacterial effect
16 Floxuridine Image 17 Anti-tumor
17 Tigecycline Image 18 Anti-bacterial
18 Pemetrexed Image 19 Anti-tumor
19 L(+)-Ascorbic acid Image 20 Anti-scorbutic
20 Glutathione Image 21 Treatment of hepatic disease
21 Hesperetin Image 22 Anti-oxidation, anti-virus,
anti-bacteria
22 Ademetionine Image 23 Cholagogue
23 Masoprocol Image 24 Treatment of actinic keratosis
24 Isotretinoin Image 25 Anti-tumor
25 Dantrolene Image 26 Muscle relaxant
26 Sulfasalazine Image 27 Anti-bacterial effect
27 Silybin Image 28 Hepatoprotective effect
28 Nicardipine Image 29 Anti-hypertensive effect
29 Sildenafil Image 30 Treatment of erectile dysfunction


----



Table 2. Potential PLpro inhibitors from in-house natural product database.

No. Compound name Structure Pharmacological function Source
1 Platycodin D Image 31 Anti-tumor, anti-inflammatory effect Platycodon grandiflorus
2 Chrysin Image 32 Anti-virus, anti-inflammatory effect Scutellaria baicalensis
3 Neohesperidin Image 33 Anti-tumor, anti-allergic effect Citrus aurantium L.
4 Baicalin Image 34 Anti-tumor, anti-inflammatory, anti-bacterial, anti-virus effect Scutellaria baicalensis
5 Sugetriol-3,9-diacetate Image 35 Anti-HBV,
Anti-HSV-1 Cyperus rotundus
6 (–)-Epigallocatechin gallate Image 36 Anti-oxidation, anti-tumor, treatment of depression Camellia sinensis
7 Phaitanthrin D Image 37 Anti-virus Isatis indigotica Fort.
8 2-(3,4-Dihydroxyphenyl)-2-[[2-(3,4-dihydroxyphenyl)-3,4-dih​ydro-5,7-dihydroxy-2H-1-benzopyran-3-yl]oxy]-3,4-dihydro-2H-1​-benzopyran-3,4,5,7-tetrol Image 38 Anti-oxidant, anti-inflammatory, anti-tumor Vitis vinifera
9 2,2-Di(3-indolyl)-3-indolone Image 39 Anti-virus Isatis indigotica Fort.
10 (S)-(1S,2R,4aS,5R,8aS)-1-Formamido-1,4a-dimethyl-6-methyle​ne-5-((E)-2-(2-oxo-2,5-dihydrofuran-3-yl)ethenyl)decahydronap​hthalen-2-yl-2-amino-3-phenylpropanoate Image 40 Anti-virus, anti-inflammatory effect Andrographolide derivatives
11 Piceatannol Image 41 Anti-tumor, anti-virus effect Vitis vinifera
12 Rosmarinic acid Image 42 Anti-virus,
Anti-oxidant Salvia verticillata L.
13 Magnolol Image 43 Anti-tumor,
Anti-microbial effect Magnolia officinalis





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We have identified a number of compounds that might have anti-viral activity from the approved drugs library, such as anti-virus drugs (ribavirin, valganciclovir and thymidine), anti-bacterial drugs (cefpiramide, sulfasalazine, phenethicillin, lymecycline, demeclocycline, doxycycline, oxytetracycline and tigecycline), anti-asthmatic drugs (montelukast, fenoterol and reproterol), and hepatoprotective drug silybin. The original pharmacological actions of these drugs could be helpful for the therapy of viral infection pneumonia. The natural products, such as flavanoids like neohesperidin, hesperidin, baicalin, kaempferol 3-O-rutinoside and rutin from different sources, andrographolide, neoandrographolide and 14-deoxy-11,12-didehydroandrographolide from Andrographis paniculata, and a series of xanthones from the plants of Swertia genus, with anti-virus, anti-bacteria and anti-inflammation activity could effectively interact with these targets of SARS-CoV-2. Therefore, the herbal medicines containing these compounds as major components might be meaningful for the treatment of SARS-CoV-2 infections.

For ACE2 target, although several compounds could bind with ACE2 through virtual screening in our studies, no compound was found to bind with the contact surface of ACE2–Spike complex, suggesting that these compounds are only the inhibitors of ACE2 enzyme activities, rather than inhibitors of ACE2 driven virus infections. Just like what described in recently published research53, most of selected compounds are also unable to bind with the contact surface of ACE2–Spike complex. Actually, these potential ACE2 inhibitors may not be suitable to use as drugs for treating SARS-CoV-2 infection because the poor prognosis would be induced by the inhibition of ACE2 enzyme activities, for ACE2 was considered as a protective factor of lung injury54.

For those targets which are difficult to find direct inhibitors, or non-druggable targets, just like Nsp1, Nsp3b, Nsp3c, and E-channel, etc., currently popular PROTAC technology may be a good strategy to degrade these proteins and then inhibit the virus. The potential binding compounds found in this study for these targets might be a good start point.

For Spike protein, we found only one compound, natural hesperidin was targeting the binding between Spike RBD and human ACE2. However, not like the ACE2 binding compounds, non-interface binding compound may still meaningful applications, considering that the fusion of CoVs membrane with host cell membrane need the big conformational change of remained Spike part after RBD removal55. Any small molecule bound to Spike at this time may interfere the re-folding of Spike therefore inhibits the viral infection process. Furthermore, small molecule that can target any part of Spike protein may be a good start point to design PROTAC based therapy.

Also, we dock existing anti-viral drugs with our targets, analyze the possible targets of each anti-viral drug horizontally, and analyze the drugs that may interact with 21 targets vertically. We analyzed 21 targets based on the docking results and found that Nsp3b, Nsp3c, Nsp7_Nsp8 complex, Nsp14, Nsp15, PLpro, 3CLpro, RdRp, helicase, E-channel, Spike and ACE2 are more likely to be therapeutic targets of anti-viral drugs. The three targets Nsp3b, Nsp3c, and E-channel are screened more anti-viral drugs. This may be due to the model problem because of flexible small protein (Nsp3b and Nsp3c) or partial model (E-channel). Whether the screened anti-viral drugs really work on these targets needs further verification. We also do not recommend the application of new coronavirus pneumonia to compounds for which no target has been predicted.

The triphosphate nucleotide product of remdesivir, remdesivir-TP, competes with RdRp for substrate ATP, so it can interfere with viral RNA synthesis. Our docking results show that remdesivir-TP binds to SARS-CoV-2 RdRp, with a score of –112.8, and the docking results are consistent with its original anti-viral mechanism, so we think remdesivir may be good in treating SARS-CoV-2 pneumonia. In addition, remdesivir also predicted to bind with the human TMPRSS2, a protein facilitating the virus infection, this is a new discovery and provides ideas for subsequent research.

Chloroquine phosphate has shown better anti-SARS-CoV-2 effects in recent studies, but this drug has no clear target of action. In our docking results, chloroquine phosphate is predicted to possibly combine with Nsp3b and E-channel. But we need to do further experiments to verify this conclusion.

In response to the recently reported anti-AIDS drugs lopinavir and ritonavir tablets, which have a poor effect on the treatment of novel coronavirus pneumonia and have toxic side effects, we analyzed it in conjunction with the docking results. The molecular docking results show that ritonavir’s possible target is Nsp3c or E-channel. Lopinavir’s possible target is Nsp3b, Nsp3c, helicase, NRBD or E-channel. Some of these targets (such as Nsp3b, Nsp3c, E-channel) may be false positives due to the model inaccuracy for small flexible protein or partial model. For both lopinavir and ritonavir, we did not observe possible binding to major targets like 3CLpro, PLpro, RdRp, and so on. This docking result implies lopinavir and ritonavir tablets may not be suitable for treatment of SARS-CoV-2 infections.

The results of the entire article are based on computer virtual screening. We have not conduct further in vivo and in vitro anti-viral experiments yet, because we want to share our results with scientists in anti-SARS-CoV-2 research as soon as possible. Our subsequent research will try to solve the three-dimensional structures of all 24 proteins of SARS-CoV-2 and their drug complexes, providing more target information for drug intervention and long-term drug design, perform in vivo and in vitro evaluations for candidate drugs obtained in this study, and prepare for clinical trial applications.






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citrus and peel, OJ by the bottle
Apartame! - wtf!
Skullcap!
Andrographis herb
chloroquine anti-malarial as the big guns

[link to www.beneficialbotanicals.com (secure)]

Label: Beneficial Botanicals
Botanical Name: Sambucus nigra (black elderberry)
Other Names: Elder, S. Nigra (European), S. Melanocarpa or spp. cerulea (North American)
Parts Used: fresh berries
Organic: Yes
Tincture Ratio: 1:2
Alcohol by Volume: 29%
Origin: USA

black-elderberry-sambucus-nigra
Known Uses:
rhinovirus (cold virus, no fever), rhinitis prevention
H1N1 (Swine Flu Virus)
H5N1 (Avian Flu Virus)
autoimmune disorders

[tab name="Overview"]

Antiviral / Anti-inflammatory / Antirheumatic / Antioxidant / Diuretic

Laboratory trials during 2005 at a research institute in London resulted in findings that Black Elderberry is 99% effect against the Avian Flu (H5N1) virus. During the flu epidemic in Panama in 1995, Elderberry juice was used to treat people with the flu virus. At the Bundesforschungsanstalt research center in Karlsruhe, Germany, scientists conducting studies on Elderberry showed that elderberry anthocyanins enhanced immune function by boosting the production of cytokines. These unique proteins act as messengers in the immune system to help regulate immune response, thus helping to defend the body against disease. Further research indicated that anthocyanins found in Elderberries possess appreciably more antioxidant capacity than either vitamin E or vitamin C. According to the University of Maryland Medical Center, Elderberry may decrease swelling in mucous membranes, such as the sinuses, and relieve nasal congestion.

How It Works As An Antiviral
The proteins actually prevent the virus from invading the cell. The influenza virus invades cells by puncturing the cell wall with the tiny spikes of hemaGglutinin that cover its surface. The active ingredient in the elderberry disarms these the spikes, binds to them, thus stopping them from piercing the cell membrane. Evidence also showed that elderberry proteins fight the influenza virus in another way, too. The viral spikes are covered with the enzyme, neuraminidase, which helps break down the healthy cell wall. The elderberry inhibits the action of the enzyme. -- Dr. Madeleine Mumcuoglu (world-renowned Israeli virologist)

Constituents-Chemicals and Nutrients:
The fruit contains flavonoids, including rutin, quercitrin and kaempferol etc., phenolic acids, e.g. chlorogenic acid, pectin, and sugars. The leaves contain triterpenes similar to those found in the flowers. Cyanogenetic glycosides, and sambunigrin and flavonoids including rutin and quercitin, fatty acids, alkanes, tannins. The bark contains phytohaemagglutinins.

[link to downloads.hindawi.com]

Antiviral Protein of Momordica charantia L. Inhibits
Different Subtypes of Influenza A


1. Introduction
Influenza A viruses have continued to be a significant public
health concern with epidemics responsible for serious morbidity and mortality. Epidemics of influenza occur almost
every year according to an antigenic drift of the two viral surface glycoproteins, hemagglutinin (HA), and neuraminidase
(NA). Currently, sixteen hemagglutinin subtypes (H1–H16)
and nine neuraminidase subtypes (N1–N9) have been recognized [1]. In the year 1918, the highly pathogenic strains of
influenza A virus emerged in an unpredictable manner, causing the death of 20–40 million people worldwide [2, 3].
Pandemic strains of the virus usually possess antigenically
different, novel glycoproteins, causing the limitation of duration and cross strain protection of currently available vaccines. For example, the emerging strains of avian influenza
viruses (H5N1) appeared in humans in Hong Kong in
1997 [4]. These viruses had an extremely high virulence in
humans, killing 6 out of 18 infected individuals. Recently, the
outbreak of influenza A/H5N1 infection has occurred among
poultry in Asia and had transmission to 499 people in 15
countries with a high case fatality rate of approximately 60%
[5]. According to the report of WHO on April 14, 2013, a new
influenza virus H7N9 emerges in eastern China and possibly
spreads into Vietnam, causing at least 13 deaths among 60
infections.
Presently, the two inhibitors of the M2 protein, amantadine, and rimantadine and the two neuraminidase inhibitors,
zanamivir and oseltamivir are the available anti-influenza A
agents [6]. However, up to 30% of individuals who received
amantadine or rimantadine excreted viral resistant strains [7,
8]. Additionally, many reports indicated that neuraminidase
inhibitor resistant strains arose rapidly in the presence of
therapeutic agents

[link to www.jstage.jst.go.jp (secure)]

Lectins as Bioactive Proteins in Foods and Feeds
Koji Muramoto




...


Immunomodulating effects
Nowell's discovery of the mitogenic activity of PHA on lymphocytes had a huge impact on various research fields, including immunology and cell biology, since lymphocytes had previously been regarded as terminal cells that could neither divide nor differentiate (Sharon and Lis, 1998). Since then, many mitogenic lectins have been isolated and characterized. These lectins are taken up into the gut barrier and subsequently transported throughout the body, resulting in antibody production and other immunological effects. PHA and several other common lectins induced human basophils to secrete interleukin-4 (IL-4) and IL-13, the key promoters of T helper type (Th2) cell responses and IgE synthesis (Vasconcelos and Oliveira, 2004).

Garlic (Allium sativum), an important medicinal spice, displays a plethora of biological effects, including immunomodulation. Garlic lectins, ASA I and ASA II, are contained in the bulb as major proteins, and belong to the monocot mannose-specific lectins. Garlic lectins non-specifically activated mast cells and basophils in atopic subjects as a result of the higher density of IgE (Clement et al., 2010). More atopic subjects showed positive reaction in the skin prick test using garlic lectins than non-atopic (normal) subjects. These results suggest that ASAs are potent mitogens with potential utility in therapeutic immunomodulation, especially because they are derived from a safe dietary source. Lectins from other Allium sp. exert similar immunomodulating effects (Yamazaki et al., 2016).

Antimicrobial activity

Mannose-binding lectins exhibit significant activity against human immunodeficiency virus (HIV) and other viruses with an envelope (Akkouh et al., 2015). Viral envelope glycoproteins such as gp41 and gp120 cover the surfaces of retroviruses such as HIV and many other viruses. Since these envelope glycoproteins are heavily glycosylated with mannose residues, mannose-binding lectins interfere with viral attachment in the early stage of the replication cycle and suppress growth by interacting at the end of the virus infectious cycle. The mannose-binding lectins from cyanobacteria and algae display high anti-HIV potencies with nanomolar-picomolar IC50 values (Hirayama et al., 2016). Banana (Musa acuminata) lectin was observed to directly bind gp120 and block cellular entry of HIV, thereby suppressing HIV infection (Swanson et al., 2010).


........


Quick retraction of a faulty coronavirus paper was a good moment for science

[link to www.statnews.com (secure)]

Titled “Uncanny similarity of unique inserts in the 2019-nCoV spike protein to HIV-1 gp120 and Gag,” the paper claimed to find similarities between the new coronavirus and HIV, the virus that causes AIDS. The use of the word “uncanny” in the title, together with “unlikely to be fortuitous” in the abstract, led some to think that the authors were suggesting the virus had somehow been engineered by humans.

The paper, from academic institutions in New Delhi, India, was critical and alarming, if true. Except that it wasn’t.

The paper was almost immediately withdrawn,

[link to www.nature.com (secure)]

The HIV envelope glycoprotein gp120.
From: Targeting the glycans of glycoproteins: a novel paradigm for antiviral therapy

Ribbon diagrams showing the 24 putative N-glycosylation sites (coloured circles) in the HIV-1(IIIB) envelope glycoprotein gp120 according to Kwong et al.123 and Leonard et al.87 a | High-mannose-type (green) and complex or hybrid-type (yellow) glycans. b | The red circles indicate the deleted N-glycosylation sites that appear under pressure from carbohydrate-binding agents (CBAs) (for example, Galanthus nivalis agglutinin (GNA), Hyppeastrum hybrid agglutinin (HHA), Urtica dioica agglutinin (UDA), cyanovirin-N (CV-N), pradimicin A (PRM-A) and the monoclonal antibody 2G12) in more than 30 different mutant virus isolates. The green circles represent glycosylation sites that have not yet been found to be deleted under CBA pressure12



1. CBA with proven anti-HIV activity in cell culture

[link to journals.sagepub.com (secure)]




[link to plantmedicines.org (secure)]

Mannose-binding Lectins from Plants

Speaking of SARS, an important study from The Netherlands’ University of Gent studied plant-derived mannose-binding lectins on SARS (severe acute respiratory syndrome) coronavirus and the feline infectious peritonitis virus (FIPV).

The researchers studied known plant lectins from 33 different plants. The researchers utilized Vero E6 cells to determine the ability of these lectins to inhibit the replication of the two viruses.



Those antiviral lectins were successful in inhibiting the replication of the viruses.

Here is the list of the mannose-binding plant lectins that were antiviral against both the SARS and FIPV viruses from the research:

Amaryllis (Hippeastrum hybrid)
Snowdrop (Galanthus nivalis)
Daffodil (Narcissus pseudonarcissus)
Red spider lily (Lycoris radiate)
Leek (Allium porrum)
Ramsons (Allium ursinum)
Taro (Colocasia esculenta)
Cymbidium orchid (Cymbidium hybrid)
Twayblade (Listera ovata)
Broad-leaved helleborine (Epipactis helleborine)
Tulip (Tulipa hybrid)
Black mulberry tree (Morus Nigra)
The other plant lectins that were antiviral against both included:
Tabacco plant (Nicotiana tabacum)
Stinging nettle (Urtica dioica)

In my previous paper, I investigated the research on two species of red algae shown to contain mannose-binding lectins having antiviral properties against herpes, HIV, Hepatitis-C and Ebola, as well as SARS. These viruses have similar glycoprotein envelopes.

[link to www.ncbi.nlm.nih.gov (secure)]

Inhibition of severe acute respiratory syndrome coronavirus replication in a lethal SARS-CoV BALB/c mouse model by stinging nettle lectin, Urtica dioica agglutinin




...



We have demonstrated the potent inhibition of SARS-CoV replication in cell culture by neutral red uptake assay and virus yield reduction assay. We have also shown that UDA inhibited retroviral particles pseudotyped with SARS-CoV spike (S) infection in vitro, suggesting that a function of SARS-CoV spike (S) protein might be targeted by UDA. This in vitro inhibitory activity also translated into inhibition of virus-induced mortality in a lethal SARS-CoV challenge model of mice, but did not reduce the virus lung titers. One possibility to explain the efficacy of UDA in spite of not significantly reducing virus titers may be attributed to the putative mechanism of action supported by the data previously described. It is likely that UDA inhibits attachment and thus limits spread of virus from infected cells to uninfected cells by binding to released virus to prevent attachment to uninfected cells.


...

The angiotensin-converting enzyme 2 (ACE2) has been identified as a functional receptor for SARS-CoV (Li et al., 2003). CD209L (also called L-SIGN, DC-SIGNR, and DC-SIGN2), a different human cellular glycoprotein, has been demonstrated as an alternative receptor for SARS-CoV (Jeffers et al., 2004). Plant lectins are sugar-binding proteins with high affinity for their specific sugar residues and play important roles in biological recognition phenomena involving cells and proteins. Some viruses use lectins to attach themselves to the host cells to initiate infection (Jeffers et al., 2004). SARS-CoV antigens have been detected in alveolar epithelial cells (primarily type II pneumocytes), bronchial epithelial cells, and alveolar macrophages of the respiratory tract (Ding et al., 2004; Ye et al., 2007). All of these cell types have ACE2 (Li et al., 2003). CD209L is expressed in human lung on type II alveolar cells and can mediate infection by SARS-CoV (Jeffers et al., 2004). SARS-CoV spike (S) glycoprotein attach to use both ACE2 and CD209L in the early steps of viral infection. Because previous studies have shown that SARS-CoV spike (S) glycoprotein binds to the cell surface lectins DC-SIGN and DC-SIGNR (Marzi et al., 2004; Yang et al., 2004), it needs to be further determined whether UDA blocks binding of SARS-CoV to DC-SIGN and DC-SIGNR. The in vitro data suggest that the mode of inhibition of the lectin UDA might be binding to the virion to prevent adsorption, perhaps by UDA binding to the epitope found on the SARS-CoV spike protein that binds to DC-SIGN and DC-SIGNR.

[link to www.hindawi.com (secure)]

Lectins as Promising Therapeutics for the Prevention and Treatment of HIV and Other Potential Coinfections



3.4. Lectins with Inhibitory Activities against Coronaviruses

Coronaviruses constitute an important class of human and animal pathogens, and some have been assessed for their susceptibility to lectins. Interestingly, GRFT also prevents SARS coronavirus (SARS-CoV) infection in vitro and in vivo, through specific binding to its spike glycoprotein, and shows activity against multiple other coronaviruses pathogenic to humans, other mammals, and birds; in mice, these inhibitory effects were accompanied with a specific inhibition of deleterious host immune reactions in response to SARS [85]. The Middle East respiratory syndrome coronavirus (MERS-CoV), another highly pathogenic human coronavirus, is inhibited at the entry level by GRFT to prevent infection in vitro [86]. In addition, Hippeastrum hybrid agglutinin (HHA), GNA, Cymbidium agglutinin (CA), and Urtica dioica agglutinin (UDA) demonstrate antiviral activities against coronaviruses in vitro and/or in vivo [67]. In an impressive screening of 33 plant lectins, remarkable antiviral effects on both SARS-CoV and feline infectious peritonitis virus (FIPV) with EC50 values at low μg/ml levels were observed, with strongest activities found predominantly among mannose-binding lectins [66]. Based on these data, lectins should be included in antiviral strategies to fight SARS coronavirus infections [87].




[link to www.sciencedirect.com (secure)]


The most potent lectin against the SARS-CoV-induced cytopathicity is the mannose-specific plant lectin isolated from leek (APA) with an EC50 of 0.45 μg/ml and a selectivity index of >222. In addition, the N-acetyl glucosamine-specific lectins isolated from the stinging nettle (UDA) and from the tobacco plant (Nictaba) are also markedly active against the SARS-CoV with a selectivity index of >77 and >59, respectively. F

Plant lectins are potent inhibitors of coronaviruses by interfering with two targets in the viral replication cycle

Nettle

timestamp link
[link to youtu.be (secure)]

[link to docs.google.com (secure)]

An Effective Treatment for Coronavirus (COVID-19)


Presented by: James M. Todaro, MD (Columbia MD, and Gregory J. Rigano, Esq.

In consultation with Stanford University School of Medicine, UAB School of Medicine and National Academy of Sciences researchers.


March 13, 2020

Summary


Recent guidelines from South Korea and China report that chloroquine is an effective antiviral therapeutic treatment against Coronavirus Disease 2019. Use of chloroquine (tablets) is showing favorable outcomes in humans infected with Coronavirus including faster time to recovery and shorter hospital stay. US CDC research shows that chloroquine also has strong potential as a prophylactic (preventative) measure against coronavirus in the lab, while we wait for a vaccine to be developed. Chloroquine is an inexpensive, globally available drug that has been in widespread human use since 1945 against malaria, autoimmune and various other conditions.

Protecting Yourself and Your Family from Coronavirus
[link to www.glutenfreesociety.org (secure)]

[link to journals.plos.org (secure)]

Zn2+ Inhibits Coronavirus and Arterivirus RNA Polymerase Activity In Vitro and Zinc Ionophores Block the Replication of These Viruses in Cell Culture

Thread: ACE 2 inhibitor medication- enalapril, etc and sudden falls out CV (Page 3)

[link to www.preprints.org (secure)]

Revealing the Potency of Citrus and Galangal Constituents
to Halt SARS-CoV-2 Infection


Rohmad Yudi Utomo1,2, Muthi’ Ikawati1,3, Edy Meiyanto1,3,*
1Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada (UGM),
Sekip Utara, Yogyakarta 55281, Indonesia
2Medicinal Chemistry Laboratory, Department of Pharmaceutical Chemistry, Faculty of Pharmacy,
UGM, Sekip Utara, Yogyakarta 55281, Indonesia
3Macromolecular Engineering Laboratory, Department of Pharmaceutical Chemistry, Faculty of
Pharmacy UGM, Sekip Utara, Yogyakarta 55281, Indonesia
*


ORCID:
Edy Meiyanto: 0000-0002-0886-6322
Rohmad Yudi Utomo: 0000-0003-4803-9417
Muthi’ Ikawati: 0000-0002-5968-0130

Abstract

COVID-19 pandemic is a serious problem in the world today. The SARS-CoV-2 virus that causes
COVID-19 has important proteins used for its infection and development, namely the protease and
spike glycoprotein. The RBD (Receptor Binding Domain) of spike glycoprotein (RBD-S) can bind to the
ACE2 (Angiotensin Converting Enzyme-2) receptor at the protease domain (PD) (PD-ACE2) of the host
cell, thereby leading to a viral infection. This study aims to reveal the potential of compounds contained
in Curcuma sp., Citrus sp., Alpinia galanga, and Caesalpinia sappan as anti SARS-CoV-2 through its
binding to 3 protein receptors. The study was conducted by molecular docking using the MOE 2010
program (licensed from Faculty of Pharmacy UGM, Indonesia). The selected protein targets are RBDS (PDB ID:6LXT), PD-ACE2 (PDB ID: 6VW1), and SARS-CoV-2 protease (PDB ID:6LU7). The affinities
of bonds formed is represented as a docking score. The results show that hesperidin, one of the
compounds in Citrus sp., has the lowest docking score for all three protein receptors representing the
highest affinity to bind the receptors. Moreover, all of the citrus flavonoids possess good affinity to the
respected receptors as well as curcumin, brazilin, and galangin, indicating that those compounds
perform inhibitory potential for the viral infection and replication. In general, the results of this study
indicate that Citrus sp. exhibit the best potential as an inhibitor to the development of the SARS-CoV2, followed by galangal, sappan wood, and Curcuma sp. that can be consumed in daily life as
prophylaxis of COVID-19.
Keywords: SARS-CoV-2; Citrus sp., Galangal, Curcuma sp., Sappan wood


All these data represent the potential inhibitory effect of Citrus sp., Curcuma sp., C. sappan, and A.
galanga on SARS-CoV-2 infection and development that may be addressed for treatment and
prevention of COVID-19. Based on the docking scores of the constituents, Citrus sp. showed the best
potency, followed by A. galanga, sappan wood, and Curcuma sp. Noted for Curcuma sp. and sappan
wood which are the main ingredients of most Indonesian traditional medicine “jamu” formulas, it is
commonly believed to contribute in maintaining health condition due to its antioxidant activities of their
constituents, such as curcumin in curcuma rhizome and brazilin in sappan wood (Meiyanto & Larasati,
2019). People usually consume these herbs in various drinking herbal formulas. This finding supports
the use of those medicinal plants for preventive or prophylaxis treatment against beta corona virus
infection, including SARS-CoV-2. The same antiviral potency also performed by galangal which mainly
contain galangin. Galangal has been used as spices for several food and exhibit pharmacological
benefit as anti-ageing (Ahlina et al., 2020). This finding gives us to the additional benefit of this herb for
antiviral.

Showing all foods in which the polyphenol Hesperidin is found

[link to phenol-explorer.eu]

Orange [Blood], juice from concentrate 51.30 mg/100 ml

Peppermint, dried 480.65 mg/100 g

[link to www.preprints.org (secure)]

Revealing the Potency of Citrus and Galangal Constituents to Halt SARS-CoV-2 Infection



Hesperedin - citrus... peppermint
Glycyrrhizin - licorice
Baicalin - skullcap, Scutellarin - skullcap


Other natural occurring compounds
Baicalin SARS-CoV-2 Binds to ACE2 receptor (in silico) Chen & Du,
2020
Scutellarin SARS-CoV-2 Binds to ACE2 receptor (in silico) Chen & Du,
2020
Glycyrrhizin SARS-CoV-2 Binds to ACE2 receptor (in silico) Chen & Du,
2020
Herbacetin SARS-CoV Binds to SARS-CoV 3CLpro (in silico)
and inhibits its activity (in vitro)
Jo et al., 2020
Rhoifolin SARS-CoV Binds to SARS-CoV 3CLpro (in silico) Jo et al., 2020
Pectolinarin SARS-CoV Binds to SARS-CoV 3CLpro (in silico) Jo et al., 2020
Galangin Herpes simplex virus type 1
(HSV-1)
High antiviral activity Mayer et al.,
1997
Coxsackie B virus type 1
(Cox B1)
High antiviral activity

yawn for victory




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[link to my.clevelandclinic.org (secure)]

What is the Diaphragm?
The diaphragm is the most efficient muscle of breathing. It is a large, dome-shaped muscle located at the base of the lungs.

What is diaphragmatic breathing?
Diaphragmatic breathing is intended to help you use the diaphragm correctly while breathing to:

Strengthen the diaphragm
Decrease the work of breathing by slowing your breathing rate
Decrease oxygen demand
Use less effort and energy to breathe