scholarly journals In Vitro Assessment of the Antiviral Activity of Ketotifen, Indomethacin and Naproxen, Alone and in Combination, against SARS-CoV-2

Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 558
Author(s):  
Pantea Kiani ◽  
Andrew Scholey ◽  
Thomas A. Dahl ◽  
Lauren McMann ◽  
Jacqueline M. Iversen ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Severe Acute Respiratory Syndrome ◽  
Antiviral Activity ◽  
Synergistic Effect ◽  
Treatment Options ◽  
Drug Combinations ◽  
Cytotoxic Effects ◽  
Viral Yield ◽  
In Vitro Assessment

The 2019 coronavirus infectious disease (COVID-19) is caused by infection with the new severe acute respiratory syndrome coronavirus (SARS-CoV-2). Currently, the treatment options for COVID-19 are limited. The purpose of the experiments presented here was to investigate the effectiveness of ketotifen, naproxen and indomethacin, alone or in combination, in reducing SARS-CoV-2 replication. In addition, the cytotoxicity of the drugs was evaluated. The findings showed that the combination of ketotifen with indomethacin (SJP-002C) or naproxen both reduce viral yield. Compared to ketotifen alone (60% inhibition at EC50), an increase in percentage inhibition of SARS-CoV-2 to 79%, 83% and 93% was found when co-administered with 25, 50 and 100 μM indomethacin, respectively. Compared to ketotifen alone, an increase in percentage inhibition of SARS-CoV-2 to 68%, 68% and 92% was found when co-administered with 25, 50 and 100 μM naproxen, respectively. For both drug combinations the observations suggest an additive or synergistic effect, compared to administering the drugs alone. No cytotoxic effects were observed for the administered dosages of ketotifen, naproxen, and indomethacin. Further research is warranted to investigate the efficacy of the combination of ketotifen with indomethacin (SJP-002C) or naproxen in the treatment of SARS-CoV-2 infection in humans.

scholarly journals In Vitro Assessment of Efficacy and Cytotoxicity of Prunus africana Extracts on Prostate Cancer C4-2 Cells

2021 ◽  
Author(s):  
Peace C. Asuzu ◽  
Alberta N.A. Aryee ◽  
Nicholas Trompeter ◽  
Yasmin Mann ◽  
Samuel A. Besong ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lncap Cells ◽  
Leaf Extracts ◽  
Cytotoxic Effects ◽  
Prunus Africana ◽  
Plant Parts ◽  
Dependent Inhibition ◽  
Hormone Sensitive ◽  
In Vitro Assessment

AbstractPhenolic compounds are products of secondary plant metabolism known for their biological activity including their antimicrobial, antioxidant, analgesic, stimulant, anti- carcinogenic, and aphrodisiac properties. The main objective of this study was to assess the potency/cytotoxic effects of Prunus africana extracts on prostate cancer cells in vitro. Using different concentrations of P. africana extracts, prostate cancer C4-2 cells, a hormonally insensitive subline of LNCaP cells, were treated in a proliferation assay. A concentration dependent inhibition of cell growth in cells treated with P. africana bark and root extracts was present from days 1 through 3 of incubation, with the methanol extract of the bark showing the strongest effect. Compared to other plant parts, leaf extracts were significantly less cytotoxic at the same concentrations. As C4-2 cells are hormonally insensitive and designed to mimic advanced prostate cancer, crude extracts of P. africana are a possible treatment option, not only for hormone sensitive prostate cancer, but also advanced, hormonally insensitive prostate cancer.

scholarly journals In vitro assessment of the genotoxic and cytotoxic effects of boiled juice (tucupi) from Manihot esculenta Crantz roots

2016 ◽  
Vol 15 (4) ◽  
Author(s):  
L.A. Cunha ◽  
T.C. Mota ◽  
P.C.S. Cardoso ◽  
D.D.F.A. Alcântara ◽  
R.M.R. Burbano ◽  
...  
Keyword(s):  
Manihot Esculenta ◽  
Manihot Esculenta Crantz ◽  
Cytotoxic Effects ◽  
In Vitro Assessment

scholarly journals In Vitro Assessment of Anthelmintic Activities ofRauwolfia vomitoria(Apocynaceae) Stem Bark and Roots against Parasitic Stages ofSchistosoma mansoniand Cytotoxic Study

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Emmanuel Mouafo Tekwu ◽  
Kwabena Mante Bosompem ◽  
William Kofi Anyan ◽  
Regina Appiah-Opong ◽  
Kofi Baffour-Awuah Owusu ◽  
...  
Keyword(s):  
Neglected Tropical Diseases ◽  
Anthelmintic Activity ◽  
Stem Bark ◽  
Assay Method ◽  
Cytotoxic Effects ◽  
Chang Liver Cell ◽  
Plant Parts ◽  
In Vitro Assessment ◽  
Rauwolfia Vomitoria

Schistosomiasis is a Neglected Tropical Diseases which can be prevented with mass deworming chemotherapy. The reliance on a single drug, praziquantel, is a motivation for the search of novel antischistosomal compounds. This study investigated the anthelmintic activity of the stem bark and roots ofRauwolfia vomitoriaagainst two life stages ofSchistosoma mansoni. Both plant parts were found to be active against cercariae and adult worms. Within 2 h of exposure all cercariae were killed at a concentration range of 62.5–1000 µg/mL and 250–1000 µg/mL ofR. vomitoriastem bark and roots, respectively. The LC50values determined for the stem bark after 1 and 2 h of exposure were 207.4 and 61.18 µg/mL, respectively. All adult worms exposed to the concentrations range of 250–1000 µg/mL for both plant parts died within 120 h of incubation. The cytotoxic effects against HepG2 and Chang liver cell assessed using MTT assay method indicated that both plant extracts which were inhibitory to the proliferation of cell lines with IC50> 20 μg/mL appear to be safe. This report provides the first evidence of in vitro schistosomicidal potency ofR. vomitoriawith the stem bark being moderately, but relatively, more active and selective against schistosome parasites. This suggests the presence of promising medicinal constituent(s).

scholarly journals A Scientific Symposium “Artificial Organs Today: From in Vitro Assessment to Human Therapies” on the Occasion of the Celebration of the 40th Anniversary of the Macedonian Academy of Sciences and Arts

PRILOZI ◽  
2020 ◽  
Vol 41 (3) ◽  
pp. 91-93
Author(s):  
Momir H. Polenakovic
Keyword(s):  
Treatment Options ◽  
Artificial Organs ◽  
Artificial Organ ◽  
40Th Anniversary ◽  
System Requirements ◽  
In Vitro Assessment ◽  
Academy Of Sciences ◽  
Organ Replacement ◽  
Ageing Populations

AbstractOn the occasion of the celebration of the 40th anniversary of the Macedonian Academy of Sciences and Arts (MASA) the Macedonian Society of Nephrology, Dialysis, Transplantation and Artificial Organs (MSNDTAO) organized a one day symposium titled: “Artificial Organs Today: From in vitro assessment to human therapies”, on September 28, 2007 at the Macedonian Academy of Sciences and Arts. The following sessions were held: Artificial Organs in Front of the Ageing Populations; System Requirements for Artificial Organ Technology; Tools for Artificial Organ Technology; Extracorporeal Blood Circuits in Organ Replacement Therapies; Treatment Options for Blood Purification Therapies. Presentation were delivered by: Horst Klinkmann, Germany; Jörg Vienken, Germany; Jens Hartmann, Austria; Udo Losert, Austria; Jan Wojcicki, Poland; Helmut Mann and Siegfried Stiller, Germany; Beat Walpoth, Switzerland; Juan F. del Cañizo, Spain; Borce Georgievski, Macedonia; Bernd Stegmayr, Sweden; Momir Polenakovic, Macedonia; Petar Kes, Croatia; Aleksandar Sikole, Macedonia; Wolfgang Ramlow, Germany; Dieter Falkenhagen, Austria. These meetings are significant for the application and development of the artificial organs in patients.

scholarly journals IDentif.AI: Artificial Intelligence Pinpoints Remdesivir in Combination with Ritonavir and Lopinavir as an Optimal Regimen Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

2020 ◽  
Author(s):  
Agata Blasiak ◽  
Jhin Jieh Lim ◽  
Shirley Gek Kheng Seah ◽  
Theodore Kee ◽  
Alexandria Remus ◽  
...  
Keyword(s):  
Artificial Intelligence ◽  
Severe Acute Respiratory Syndrome ◽  
Combination Therapy ◽  
Rapid Development ◽  
Drug Combinations ◽  
Drug Candidate ◽  
Optimal Drug ◽  
Order Of Magnitude ◽  
Drug Regimens

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) has led to the rapid initiation of urgently needed clinical trials of repurposed drug combinations and monotherapies. These regimens were primarily relying on mechanism-of-action based selection of drugs, many of which have yielded positive in vitro but largely negative clinical outcomes. To overcome this challenge, we report the use of IDentif.AI, a platform that rapidly optimizes infectious disease (ID) combination therapy design using artificial intelligence (AI). In this study, IDentif.AI was implemented on a 12-drug candidate therapy search set representing over 530,000 possible drug combinations. IDentif.AI demonstrated that the optimal combination therapy against SARS-CoV-2 was comprised of remdesivir, ritonavir, and lopinavir, which mediated a 6.5-fold improvement in efficacy over remdesivir alone. Additionally, IDentif.AI showed hydroxychloroquine and azithromycin to be relatively ineffective. The identification of a clinically actionable optimal drug combination was completed within two weeks, with a 3-order of magnitude reduction in the number of tests typically needed. IDentif.AI analysis was also able to independently confirm clinical trial outcomes to date without requiring any data from these trials. The robustness of the IDentif.AI platform suggests that it may be applicable towards rapid development of optimal drug regimens to address current and future outbreaks.

scholarly journals Natural Products as Potential Leads Against Coronaviruses: Could They be Encouraging Structural Models Against SARS-CoV-2?

2020 ◽  
Vol 10 (4) ◽  
pp. 171-186 ◽  
Author(s):  
Ilkay Erdogan Orhan ◽  
F. Sezer Senol Deniz
Keyword(s):  
Infectious Disease ◽  
Natural Products ◽  
Medicinal Plants ◽  
Severe Acute Respiratory Syndrome ◽  
Antiviral Activity ◽  
Plant Extracts ◽  
Vaccine Development ◽  
Genomic Sequence ◽  
Structural Models ◽  
Positive Sense

Abstract New coronavirus referred to SARS-CoV-2 has caused a worldwide pandemic (COVID-19) declared by WHO. Coronavirus disease 2019 (COVID-19) is an infectious disease with severe acute respiratory syndrome caused by coronavirus-2 (SARS-CoV-2). SARS-CoV-2 is akin to SARS-CoV, which was the causative agent of severe acute respiratory syndrome (SARS) in 2002 as well as to that of Middle East respiratory syndrome (MERS) in 2012. SARS-CoV-2 has been revealed to belong to Coronaviridiae family as a member of β-coronaviruses. It has a positive-sense single-stranded RNA with the largest RNA genome. Since its genomic sequence has a notable similarity to that of SARS-CoV, antiviral drugs used to treat SARS and MERS are now being also applied for COVID-19 treatment. In order to combat SARS-CoV-2, many drug and vaccine development studies at experimental and clinical levels are currently conducted worldwide. In this sense, medicinal plants and the pure natural molecules isolated from plants have been reported to exhibit significant inhibitory antiviral activity against SARS-CoV and other types of coronaviruses. In the present review, plant extracts and natural molecules with the mentioned activity are discussed in order to give inspiration to researchers to take these molecules into consideration against SARS-CoV-2.

scholarly journals GNS561 exhibits potent in vitro antiviral activity against SARS-CoV-2 through autophagy inhibition

2020 ◽  
Author(s):  
Philippe Halfon ◽  
Eloïne Bestion ◽  
Keivan Zandi ◽  
Julien Andreani ◽  
Jean-Pierre Baudoin ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Antiviral Activity ◽  
Antiviral Effect ◽  
Therapeutic Strategies ◽  
Multilamellar Bodies ◽  
Molecule Inhibitor ◽  
Lipophilic Molecule ◽  
Autophagic Process ◽  
Autophagy Inhibition

AbstractSince December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/2019-nCoV) has spread quickly worldwide, with more than 29 million cases and 920,000 deaths. Interestingly, coronaviruses were found to subvert and hijack the autophagic process to allow their viral replication. One of the spotlights had been focused on the autophagy inhibitors as a target mechanism effective in the inhibition of SARS-CoV-2 infection. Consequently, chloroquine (CQ) and hydroxychloroquine (HCQ), a derivative of CQ, was suggested as the first potentially be therapeutic strategies as they are known to be autophagy inhibitors. Then, they were used as therapeutics in SARS-CoV-2 infection along with remdesivir, for which the FDA approved emergency use authorization. Here, we investigated the antiviral activity and associated mechanism of GNS561, a small basic lipophilic molecule inhibitor of late-stage autophagy, against SARS-CoV-2. Our data indicated that GNS561 showed the highest antiviral effect for two SARS-CoV-2 strains compared to CQ and remdesivir. Focusing on the autophagy mechanism, we showed that GNS561, located in LAMP2-positive lysosomes, together with SARS-CoV-2, blocked autophagy by increasing the size of LC3-II spots and the accumulation of autophagic vacuoles in the cytoplasm with the presence of multilamellar bodies characteristic of a complexed autophagy. Finally, our study revealed that the combination of GNS561 and remdesivir was associated with a strong synergistic antiviral effect against SARS-CoV-2. Overall, our study highlights GNS561 as a powerful drug in SARS-CoV-2 infection and supports that the hypothesis that autophagy inhibitors could be an alternative strategy for SARS-CoV-2 infection.

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