Metallo-antiviral aspirants: Answer to the upcoming virus outbreak

Mehrotra, Ripul; Shukla, Satyendra N.; Gaur, Pratiksha

doi:10.1016/j.ejmcr.2023.100104

Cited by 4 publications

(2 citation statements)

References 87 publications

(87 reference statements)

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“…Preformed metal coordination complexes are under investigation as anti-viral agents acting by various proposed mechanisms (e.g. Marzo and Messori 2020 ; Karges and Cohen 2021 ; Pal 2021 ; Ioannou and Vlasiou 2022 ; Mehrotra et al 2023 and others). In various investigations, the distinctions between metallo-pharmaceuticals and naked ligands is often unclear.…”

Section: Stable Preformed Metallo-pharmaceuticals Are Under Investiga...mentioning

confidence: 99%

Coordination chemistry suggests that independently observed benefits of metformin and Zn2+ against COVID-19 are not independent

Lockwood

2024

Biometals

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Independent trials indicate that either oral Zn2+ or metformin can separately improve COVID-19 outcomes by approximately 40%. Coordination chemistry predicts a mechanistic relationship and therapeutic synergy. Zn2+ deficit is a known risk factor for both COVID-19 and non-infectious inflammation. Most dietary Zn2+ is not absorbed. Metformin is a naked ligand that presumably increases intestinal Zn2+ bioavailability and active absorption by cation transporters known to transport metformin. Intracellular Zn2+ provides a natural buffer of many protease reactions; the variable “set point” is determined by Zn2+ regulation or availability. A Zn2+-interactive protease network is suggested here. The two viral cysteine proteases are therapeutic targets against COVID-19. Viral and many host proteases are submaximally inhibited by exchangeable cell Zn2+. Inhibition of cysteine proteases can improve COVID-19 outcomes and non-infectious inflammation. Metformin reportedly enhances the natural moderating effect of Zn2+ on bioassayed proteome degradation. Firstly, the dissociable metformin–Zn2+ complex could be actively transported by intestinal cation transporters; thereby creating artificial pathways of absorption and increased body Zn2+ content. Secondly, metformin Zn2+ coordination can create a non-natural protease inhibitor independent of cell Zn2+ content. Moderation of peptidolytic reactions by either or both mechanisms could slow (a) viral multiplication (b) viral invasion and (c) the pathogenic host inflammatory response. These combined actions could allow development of acquired immunity to clear the infection before life-threatening inflammation. Nirmatrelvir (Paxlovid®) opposes COVID-19 by selective inhibition the viral main protease by a Zn2+-independent mechanism. Pending safety evaluation, predictable synergistic benefits of metformin and Zn2+, and perhaps metformin/Zn2+/Paxlovid® co-administration should be investigated.

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Section: Stable Preformed Metallo-pharmaceuticals Are Under Investiga...mentioning

confidence: 99%

Coordination chemistry suggests that independently observed benefits of metformin and Zn2+ against COVID-19 are not independent

Lockwood

2024

Biometals

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“…Although metal ions can bind on single and often functionally crucial protein residues, the antiviral activities of metal-based compounds have rarely been explored [176,177]. The efficacy of metallo-antiviral agents is expected to be less liable to new viral variants, thus resulting in an enormous potential for treating viral infections.…”

Section: Antiviral Activitymentioning

confidence: 99%

Biological Activities of Bismuth Compounds: An Overview of the New Findings and the Old Challenges Not Yet Overcome

Rosário,

Moreira,

Rosa

et al. 2023

Molecules

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Bismuth-based drugs have been used primarily to treat ulcers caused by Helicobacter pylori and other gastrointestinal ailments. Combined with antibiotics, these drugs also possess synergistic activity, making them ideal for multiple therapy regimens and overcoming bacterial resistance. Compounds based on bismuth have a low cost, are safe for human use, and some of them are also effective against tumoral cells, leishmaniasis, fungi, and viruses. However, these compounds have limited bioavailability in physiological environments. As a result, there is a growing interest in developing new bismuth compounds and approaches to overcome this challenge. Considering the beneficial properties of bismuth and the importance of discovering new drugs, this review focused on the last decade’s updates involving bismuth compounds, especially those with potent activity and low toxicity, desirable characteristics for developing new drugs. In addition, bismuth-based compounds with dual activity were also highlighted, as well as their modes of action and structure–activity relationship, among other relevant discoveries. In this way, we hope this review provides a fertile ground for rationalizing new bismuth-based drugs.

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A review on recent advances of iron-based macrocyclic complexes as prominent candidate for several potential applications

Gurjar,

Saini,

Kumari

et al. 2023

J IRAN CHEM SOC

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Metallo-antiviral aspirants: Answer to the upcoming virus outbreak

Cited by 4 publications

References 87 publications

Coordination chemistry suggests that independently observed benefits of metformin and Zn2+ against COVID-19 are not independent

Coordination chemistry suggests that independently observed benefits of metformin and Zn2+ against COVID-19 are not independent

Biological Activities of Bismuth Compounds: An Overview of the New Findings and the Old Challenges Not Yet Overcome

A review on recent advances of iron-based macrocyclic complexes as prominent candidate for several potential applications

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