Native High-Density Lipoproteins (HDL) with Higher Paraoxonase Exerts a Potent Antiviral Effect against SARS-CoV-2 (COVID-19), While Glycated HDL Lost the Antiviral Activity

Human high-density lipoproteins (HDL) show a broad spectrum of antiviral activity in terms of anti-infection. Although many reports have pointed out a correlation between a lower serum HDL-C and a higher risk of COVID-19 infection and progression, the in vitro antiviral activity of HDL against SARS-CoV-2 has not been reported. HDL functionality, such as antioxidant and anti-infection, can be impaired by oxidation and glycation and a change to pro-inflammatory properties. This study compared the antiviral activity of native HDL with glycated HDL via fructosylation and native low-density lipoproteins (LDL). After 72 h of fructosylation, glycated HDL showed a typical multimerized protein pattern with an elevation of yellowish fluorescence. Glycated HDL showed a smaller particle size with an ambiguous shape and a loss of paraoxonase activity up to 51% compared to native HDL. The phagocytosis of acetylated LDL was accelerated 1.3-fold by glycated HDL than native HDL. Native HDL showed 1.7 times higher cell viability and 3.6 times higher cytopathic effect (CPE) inhibition activity against SARS-CoV-2 than that of glycated HDL under 60 μg/mL (approximately final 2.2 μM) in a Vero E6 cell. Native HDL showed EC50 = 52.1 ± 1.1 μg/mL (approximately final 1.8 μM) for the CPE and CC50 = 79.4 ± 1.5 μg/mL (around 2.8 μM). The selective index (SI) of native HDL was calculated to be 1.52. In conclusion, native HDL shows potent antiviral activity against SARS-CoV-2 without cytotoxicity, while the glycation of HDL impairs its antiviral activity. These results may explain why patients with diabetes mellitus or hypertension are more sensitive to a COVID-19 infection and have a higher risk of mortality.

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Experimental evaluation of the activity of the product meflochine against coronavirus SАRS-CoV-2

10.47183/mes.2020.006 ◽

2020 ◽

Author(s):

KN Filin ◽

IA Berzin ◽

VN Bykov ◽

VD Gladkikh ◽

SYa Loginova ◽

...

Keyword(s):

Cell Culture ◽

Antiviral Activity ◽

Kidney Cell ◽

Cytopathic Effect ◽

Antiviral Effect ◽

In Vitro Experiments ◽

Monkey Kidney Cell ◽

African Green Monkey Kidney ◽

Green Monkey

When evaluating the effectiveness of the drug Mefloquine against SARS-Cov-2 coronavirus, in vitro experiments examined its toxicity for African green monkey kidney cell culture - Vero C1008, as well as antiviral activity against SARS-Cov-2, which was evaluated by suppressing the cytopathic effect the virus. A study of the toxicity of the drug Mefloquine showed that the concentration at which the drug exerts a cytopathic effect against 50% of Vero C1008 cells is 4.5 μg / ml. The maximum tolerated concentration (MTD) of Mefloquine is 2.25 μg / ml. A study of the effectiveness showed that 1 day after infection, the antiviral effect of Mefloquine was recorded when the drug was added 24 hours and 1 hour before infection with SARS-CoV-2, as well as when it was added 1 hour after infection, the cell culture was already at a concentration of 0.5 μg / ml Mefloquine at a concentration of 2 μg / ml, added to the Vero C1008 cell culture 1 hour after the introduction of SARS-CoV-2, completely blocked the action of the virus for 2 days after infection.

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Evaluation of antiviral activity of Manuka honey against SARS-CoV-2.

10.29117/quarfe.2021.0113 ◽

2021 ◽

Author(s):

Israa Elbashir ◽

Aisha Aisha Nasser J M Al-Saei ◽

Paul Thornalley ◽

Naila Rabbani

Keyword(s):

Logistic Regression ◽

Antiviral Activity ◽

Cytopathic Effect ◽

Antiviral Treatment ◽

Antiviral Effect ◽

Vero Cells ◽

Manuka Honey ◽

Virus Control ◽

Arginine Residues

Background and aims: In 2020 a global pandemic was declared caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2). The pandemic is still ongoing and continues to cause considerable mortality and morbidity world-wide and new variants of the virus are emerging. Rapid development and rollout of vaccines for SARS-CoV-2 is in progress to counter the pandemic but has been tempered by the emergence of new SARS-CoV-2 variants, many of which exhibit reduced vaccine effectiveness. To date there is no approved antiviral treatment for coronavirus disease 2019 (COVID-19). Several studies have shown that Manuka honey has virucidal/antiviral effect. Methylglyoxal (MG), a bioactive component in Manuka honey, has antiviral activity in vitro. MG may modify arginine residues in the functional domains of viral spike and nucleocapsid proteins, resulting in loss of charge, protein misfolding and inactivation. The aim of this study was to characterize the antiviral activity of Manuka honey against SARS-CoV-2 in vitro Materials and methods: Wild-type SARS-CoV-2 with titers of multiplicities of infection (MOI) 0.1 and 0.05 were incubated with 2-fold serial dilutions of 250+ Manuka honey (equivalent to 250 to 31 µM) in infection medium (Dulbecco's Modified Eagle Medium + 2% fetal bovine serum + 100 units/ml penicillin + 100 µg/ml streptomycin) for 3 h. Manuka honey treated and untreated control SARS-CoV-2 was incubated with confluent cultures of Vero cells in vitro for 1 h, cultures washed with phosphate-buffered saline and incubated in fresh infection medium at 37°C for 4 - 5 days until 70% of virus control cells displayed cytopathic effect. We also studied the effect of scavenging MG in Manuka Honey with aminoguanidine (AG; 500 µM) on virucidal activity. The antiviral activity of MG was judged by median tissue culture infectious dose (TCID50) assays. Data analysis was by logistic regression. TCID50 (mean ± SD) was deduced by interpolation. Results: Diluted Manuka honey inhibited SARS-CoV-2 replication in Vero cells. SARS-CoV-2 was incubated in diluted Manuka honey in medium at 37°C for 3 h before adding to Vero cells. Manuka honey dilutions down to 125 µM MG equivalents completely inhibited cytopathic effect of SARS-CoV-2 whereas 31.25 µM and 62.5 µM MG equivalents had limited effect. Logistic regression and interpolation of the cytopathic effect indicated that the TCID50 = 72 ± 2 µM MG equivalents for MOI of 0.1. Prior scavenging of MG by addition of AG resulted in virus replication levels equivalent to those seen in the virus control without AG. Conclusion: Manuka honey has antiviral activity against SARS-CoV-2 when incubated with the virus in cell-free media at no greater than ca. 40-fold dilutions of 250+ grade. Anti-viral activity was inhibited by AG, consistent with the anti-viral effect being mediated by MG. Manuka honey dilutions in MG equivalents had similar antiviral effect compared to authentic MG, also consistent with MG content of Manuka honey mediating the antiviral effect. Whilst Manuka honey may inactivate SARS-CoV-2 in cell-free culture medium, its antiviral activity in vivo for other than topical application may be limited because of the rapid metabolism of MG by the glyoxalase system and limited bioavailability of oral MG.

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Relationship between High Density Lipoproteins and the Rate of In Vitro Serum Cholesterol Esterification

Scandinavian Journal of Clinical and Laboratory Investigation ◽

10.3109/00365517809104903 ◽

1978 ◽

Vol 38 ◽

pp. 72-76 ◽

Cited By ~ 1

Author(s):

Louis Soloff ◽

K. G. Varma

Keyword(s):

Serum Cholesterol ◽

High Density ◽

Cholesterol Esterification ◽

High Density Lipoproteins

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Importance of Apolipoprotein A-I and A-II Composition in HDL and Its Potential for Studying COVID-19 and SARS-CoV-2

Medicines ◽

10.3390/medicines8070038 ◽

2021 ◽

Vol 8 (7) ◽

pp. 38

Author(s):

Kyung-Hyun Cho

Keyword(s):

Antiviral Activity ◽

High Density ◽

High Density Lipoproteins ◽

Potent Antiviral Activity ◽

Apolipoprotein A ◽

Putative Role

The composition and properties of apolipoprotein (apo) A-I and apoA-II in high-density lipoproteins (HDL) might be critical to SARS-CoV-2 infection via SR-BI and antiviral activity against COVID-19. HDL containing native apoA-I showed potent antiviral activity, while HDL containing glycated apoA-I or other apolipoproteins did not. However, there has been no report to elucidate the putative role of apoA-II in the antiviral activity of HDL.

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Comparison of the cytolytic effects in vitro on Trypanosoma brucei brucei of plasma, high density lipoproteins, and apolipoprotein A-I from hosts both susceptible (cattle and sheep) and resistant (human and baboon) to infection.

The Journal of Lipid Research ◽

10.1016/s0022-2275(20)41617-7 ◽

1992 ◽

Vol 33 (4) ◽

pp. 513-523

Author(s):

MP Gillett ◽

JS Owen

Keyword(s):

Trypanosoma Brucei ◽

High Density ◽

High Density Lipoproteins ◽

Trypanosoma Brucei Brucei ◽

Apolipoprotein A ◽

Plasma High Density ◽

Cattle And Sheep

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The in vitro and in vivo potency of CT-P59 against Delta and its associated variants of SARS-CoV-2

10.1101/2021.07.23.453472 ◽

2021 ◽

Author(s):

Dong-Kyun Ryu ◽

Hye-Min Woo ◽

Bobin Kang ◽

Hanmi Noh ◽

Jong-In Kim ◽

...

Keyword(s):

Antiviral Activity ◽

Respiratory Tract ◽

Animal Studies ◽

Antiviral Effect ◽

The World ◽

Symptom Remission ◽

Challenge Experiment ◽

Reduced Activity

The Delta variant originally from India is rapidly spreading across the world and causes to resurge infections of SARS-CoV-2. We previously reported that CT-P59 presented its in vivo potency against Beta and Gamma variants, despite its reduced activity in cell experiments. Yet, it remains uncertain to exert the antiviral effect of CT-P59 on the Delta and its associated variants (L452R). To tackle this question, we carried out cell tests and animal study. CT-P59 showed reduced antiviral activity but enabled neutralization against Delta, Epsilon, and Kappa variants in cells. In line with in vitro results, the mouse challenge experiment with the Delta variant substantiated in vivo potency of CT-P59 showing symptom remission and virus abrogation in the respiratory tract. Collectively, cell and animal studies showed that CT-P59 is effective against the Delta variant infection, hinting that CT-P59 has therapeutic potency for patients infected with Delta and its associated variants.

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Evidence for the role of high density lipoproteins in mediating the antioxidant effect of estrogens

Acta Endocrinologica ◽

10.1530/eje.0.1420079 ◽

2000 ◽

pp. 79-83 ◽

Cited By ~ 15

Author(s):

W Abplanalp ◽

MD Scheiber ◽

K Moon ◽

B Kessel ◽

JH Liu ◽

...

Keyword(s):

Density Lipoprotein ◽

Antioxidant Effect ◽

High Density ◽

In Vivo Studies ◽

Ldl Oxidation ◽

High Density Lipoproteins ◽

Oh Groups

Estrogens possess strong antioxidant effects in vitro, but in vivo studies in humans have yielded conflicting results. Little is known regarding factors that mediate the antioxidant effect of estrogens in vivo. In this study the potential role of high density lipoprotein (HDL) was examined. The antioxidant effect of estradiol-17beta (E2) added to low density lipoprotein (LDL) was lost after dialysis. In contrast, the antioxidant effect of E2 added to HDL was conserved after dialysis, suggesting that E2 was bound to HDL. Binding of E2 to LDL increased after esterification (especially to long chain fatty acids). In the presence of HDL, an increased amount of E2 was transferred to LDL. E2-17 ester was as potent as E2 in preventing LDL oxidation in vitro, but 3,17-diesters were not as effective (E2=E2-17 ester>E2-3 ester>E2-3,17 diester). This was also supported by experiments which showed that estrogens with masked 3-OH groups were not effective as antioxidants. These studies provide evidence that HDL could facilitate the antioxidant effect of E2 through initial association, esterification and eventual transfer of E2 esters to LDL. Therefore it is critical that HDL peroxidation parameters be evaluated in subjects receiving estrogen replacement therapy.

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Synthesis and Evaluation of Anti-Rhinovirus 1B Activity of Oxazolinyl-Isoflavans and -3(2H)-Isoflavenes

Antiviral Chemistry and Chemotherapy ◽

10.1177/095632029200300402 ◽

1992 ◽

Vol 3 (4) ◽

pp. 195-202 ◽

Cited By ~ 16

Author(s):

N. Desideri ◽

C. Conti ◽

I. Sestili ◽

P. Tomao ◽

M. L. Stein ◽

...

Keyword(s):

Carboxylic Acid ◽

Antiviral Activity ◽

Cytopathic Effect ◽

Potent Inhibitor ◽

Therapeutic Index ◽

Intermediate Compound ◽

Plaque Formation ◽

Interesting Compound ◽

Viral Cytopathic Effect

Oxazolinyl-isoflavans and −3(2H)-isoflavenes, substituted or not with a chlorine atom, were synthesized in order to compare their anti-rhinovirus activity with that of previously studied analogous compounds. The activity of the oxazolines and of the esters and acids, which are intermediates in the synthesis, was studied in vitro against rhinovirus serotype 1B infection in HeLa cells. The ability of various non cytotoxic concentrations to interfere with the development of the viral cytopathic effect and plaque formation was examined. All the tested compounds exerted a significant antiviral activity, and most of them were as active as some representative compounds of the oxazolinyl-phenoxyalkylisoxazole (WIN) series. 6-Oxazolinylisoflavan (VI) appeared to be the most interesting compound due to its high activity and therapeutic index. Among the substituted isoflavans and isoflavenes tested so far, the intermediate compound 6-chloro-3 (2H)-isoflavene-4′-carboxylic acid (XIX) was unexpectedly the most potent inhibitor of rhinovirus 1B plaque formation.

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