Targeting TGF-β pathway with COVID-19 Drug Candidate ARTIVeda/PulmoHeal Accelerates Recovery from Mild-Moderate COVID-19

Trieu, Vuong; Saund, Saran; Barge, Viljay B.; Nalk, K. Sunil; Windlass, Hitesh; Uckun, Fatih M.

doi:10.1101/2021.01.24.21250418

Cited by 16 publications

(15 citation statements)

References 52 publications

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“…Among these four treatments, artesunate showed the strongest anti-SARS-CoV-2 activity (7-12 µg/mL), followed by artemether (53-98 µg/mL), A. annua extracts (83-260 µg/mL) and artemisinin (151 to at least 208 µg/mL). Collectively, time-ofaddition experiments in A549-hACE2 cells displayed that artesunate attacked the virus at the post-entry level [103]. Dried-leaf, hot-water extracts of A. annua cultivars (SAM, BUR, A3, and MED) revealed in vitro anti-SARS-CoV-2 activity against alpha, beta, gamma, delta, and kappa variants of the virus.…”

Section: Artemisinin and Artemisinins' Potential In Management Of Cov...mentioning

confidence: 97%

“…However, it also claims that drinking two servings per day will help consumers "maintain an active shield," thus, "protecting well-being." The firm's coffee contains 0.4 g A. annua per serving, and its tea containes 0.23 g. The dried leaves of A. annua usually contain around 1% artemisinin, therefore, consuming the drinks would offer much lower doses than typical ACTs [103].…”

Section: Artemisia Supplement and Formulationmentioning

confidence: 99%

“…With treatment, viral replication is suppressed, IFNβ is induced, and innate and adaptive immune responses are suppressed. The clinical studies on patients with mild and moderate COVID-19 have suggested that administration of artemisinin 500 mg capsules once daily for 5 days may lead to a faster recovery [103].…”

Section: Artemisia Supplement and Formulationmentioning

confidence: 99%

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RETRACTED: Artemisia Extracts and Artemisinin-Based Antimalarials for COVID-19 Management: Could These Be Effective Antivirals for COVID-19 Treatment?

Agrawal¹,

Agrawal²,

Blunden

2022

Molecules

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As the world desperately searches for ways to treat the coronavirus disease 2019 (COVID-19) pandemic, a growing number of people are turning to herbal remedies. The Artemisia species, such as A. annua and A. afra, in particular, exhibit positive effects against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and COVID-19 related symptoms. A. annua is a source of artemisinin, which is active against malaria, and also exhibits potential for other diseases. This has increased interest in artemisinin’s potential for drug repurposing. Artemisinin-based combination therapies, so-called ACTs, have already been recognized as first-line treatments against malaria. Artemisia extract, as well as ACTs, have demonstrated inhibition of SARS-CoV-2. Artemisinin and its derivatives have also shown anti-inflammatory effects, including inhibition of interleukin-6 (IL-6) that plays a key role in the development of severe COVID-19. There is now sufficient evidence in the literature to suggest the effectiveness of Artemisia, its constituents and/or artemisinin derivatives, to fight against the SARS-CoV-2 infection by inhibiting its invasion, and replication, as well as reducing oxidative stress and inflammation, and mitigating lung damage.

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Section: Artemisinin and Artemisinins' Potential In Management Of Cov...mentioning

confidence: 97%

Section: Artemisia Supplement and Formulationmentioning

confidence: 99%

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RETRACTED: Artemisia Extracts and Artemisinin-Based Antimalarials for COVID-19 Management: Could These Be Effective Antivirals for COVID-19 Treatment?

Agrawal¹,

Agrawal²,

Blunden

2022

Molecules

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“…Notably, MM cells have upregulated expression of TGF-β-activated kinase-1 (TAK1), and inhibiting TAK1 has been shown to significantly impair the growth and survival of MM cells [ 75 ]. Therefore, targeting TGF-β signaling with an RNA therapeutic such as OT101, the TGF-β targeting anti-inflammatory platforms such as RJX [ 76 ] or ArtiVeda [ 77 , 78 ] or a small molecule inhibitor such as galunisertib could contribute to sustained anti-tumor immunity and PD-1/PD-L1 responsiveness by lifting TGF-β-mediated immunosuppression.…”

Section: Targeting Transforming Growth Factor Beta (Tgf-β) Signaling and Syk-pi3k-akt Pathwaymentioning

confidence: 99%

Overcoming the Immunosuppressive Tumor Microenvironment in Multiple Myeloma

Uckun

2021

Cancers

Self Cite

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SeverFigurel cellular elements of the bone marrow (BM) microenvironment in multiple myeloma (MM) patients contribute to the immune evasion, proliferation, and drug resistance of MM cells, including myeloid-derived suppressor cells (MDSCs), tumor-associated M2-like, “alternatively activated” macrophages, CD38+ regulatory B-cells (Bregs), and regulatory T-cells (Tregs). These immunosuppressive elements in bidirectional and multi-directional crosstalk with each other inhibit both memory and cytotoxic effector T-cell populations as well as natural killer (NK) cells. Immunomodulatory imide drugs (IMiDs), protease inhibitors (PI), monoclonal antibodies (MoAb), adoptive T-cell/NK cell therapy, and inhibitors of anti-apoptotic signaling pathways have emerged as promising therapeutic platforms that can be employed in various combinations as part of a rationally designed immunomodulatory strategy against an immunosuppressive tumor microenvironment (TME) in MM. These platforms provide the foundation for a new therapeutic paradigm for achieving improved survival of high-risk newly diagnosed as well as relapsed/refractory MM patients. Here we review the scientific rationale and clinical proof of concept for each of these platforms.

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“…The median time to becoming asymptomatic was only 5 days for the SOC plus Artemisinin group (N=18) but 14 days for the SOC alone group (N=10) (P=0.004, Log-rank test). These data provide clinical proof of concept that targeting the TGF-β pathway with Artemisinin may contribute to a faster recovery of patients with mild-moderate SARS-CoV-2 when administered early in the course of their disease [35].…”

Section: Discussionmentioning

confidence: 99%

Mutational analysis of SARS-CoV-2. ORF8 and the evolution of the Delta and Omicron variants

Trieu¹,

Trieu²

2021

Preprint

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SARS-CoV-2 the virus responsible for the current pandemic. This virus is continually evolving, adapting to both innate and acquired immune responses and therapeutic drugs. Therefore, it is important to understand how the virus evolving to design the appropriate therapeutic and vaccine in preparation for future variants. Here, we used the online SARS-CoV-2 databases, Nextstrain and Ourworld, to map the evolution and epidemiology of the virus. We identified 30 high entropy residues which underwent a progressive evolution to arrive at the current dominant variant - Delta variant. The virus underwent mutational waves with the first wave made up of structural proteins important in its infectivity and the second wave made up of the ORFs important for its contagion. The most important driver of the second wave is ORF8 mutations at residue 119 and 120. Further mutations of these two residues are creating new clades that are offshoots from the Delta backbone. More importantly the further expansion of the S protein in the Omicron variant is now followed with the acquisition of ORF8 mutations 119 and 120. These findings demonstrate how SARS-CoV-2 mutates and points to two evolutionary paths; 1) Mutational expansion on the Delta backbone among the ORFs and 2) Mutational expansion of the S protein on other backbone follow with mutational wave among the ORFs. Both are happening at the same time right now with the Omicron variant early in the first wave to follow with a more aggressive second wave of mutations.

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Targeting TGF-β pathway with COVID-19 Drug Candidate ARTIVeda/PulmoHeal Accelerates Recovery from Mild-Moderate COVID-19

Cited by 16 publications

References 52 publications

RETRACTED: Artemisia Extracts and Artemisinin-Based Antimalarials for COVID-19 Management: Could These Be Effective Antivirals for COVID-19 Treatment?

RETRACTED: Artemisia Extracts and Artemisinin-Based Antimalarials for COVID-19 Management: Could These Be Effective Antivirals for COVID-19 Treatment?

Overcoming the Immunosuppressive Tumor Microenvironment in Multiple Myeloma

Mutational analysis of SARS-CoV-2. ORF8 and the evolution of the Delta and Omicron variants

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