Individualized Homeopathic Medicines in the Treatment of Post-COVID-19 Fatigue in Adults: Single-Blind, Randomized, Placebo-Controlled Trial.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) is leading to unknown and unusual health conditions that are challenging to manage. Post-COVID-19 fatigue is one of those challenges, becoming increasingly common as the pandemic evolves, as it impairs the quality of life of an individual. This trial attempts to identify the preliminary evidence of the efficacy of individualized homeopathic medicines (IHMs) against placebos in the treatment of post-COVID-19 fatigue in adults. METHODS: A 3-month, single-blind, randomized, placebo-controlled, parallel-arm trial was conducted at the outpatient department of The Calcutta Homoeopathic Medical College and Hospital, India. Sixty participants were randomized in a 1:1 ratio to receive either IHMs (n = 30) or identical-looking placebos (n = 30). The primary and secondary outcome measures were the Fatigue Assessment Scale (FAS) and Outcome in Relation to Impact on Daily Living (ORIDL), respectively, measured every month, for up to 3 months. Comparative analysis was carried out on the intention-to-treat sample to detect group differences. RESULTS: Group differences in both the primary (FAS total: F1, 58 = 14.356, p < 0.001) and secondary outcomes (ORIDL: F1, 58 = 210.986, p < 0.001) after 3 months favored IHMs against placebos. Lycopodium clavatum (11.7%), sulfur (11.7%), Arsenicum album (10%), and Thuja occidentalis (10%) were the most frequently indicated medicines. No harm, unintended effects, homeopathic aggravations, or any serious adverse events were reported from either of the groups. CONCLUSION: IHMs produced significantly better effects than placebos in the treatment of post-COVID-19 fatigue in adults. Definitive robust trials may be undertaken to confirm the findings.Die Coronainfektion (COVID-19) zieht unbekannte und ungewöhnliche gesundheitliche Probleme nach sich, deren Management oft eine Herausforderung darstellt. Das gilt unter anderem für Ermüdung nach einer COVID-19-Erkrankung, die mit zunehmender Dauer der Pandemie immer häufiger auftritt und die Lebensqualität der Betroffenen beeinträchtigt. In dieser Studie wird versucht, vorläufige Belege für die Wirksamkeit individualisierter homöopathischer Mittel (IHM) im Vergleich zu Placebo zur Behandlung von Ermüdung nach COVID-19 bei Erwachsenen zu identifizieren.Eine einfach verblindete, randomisierte, placebokontrollierte Parallelgruppenstudie von 3 Monaten Dauer wurde im ambulanten Bereich des Calcutta Homoeopathic Medical College and Hospital in Indien durchgeführt. 60 Teilnehmer erhielten nach Randomisierung im Verhältnis 1:1 entweder IHM (n = 30) oder identisch aussehendes Placebo (n = 30). Die primäre und die sekundäre Zielgröße waren die Fatigue Assessment Scale (FAS) und das Outcome in Relation to Impact on Daily Living (ORIDL) für bis zu 3 Monate, jeweils monatlich gemessen. Vergleichende Analysen wurden an der Intent-to-treat-Population durchgeführt, um Unterschiede zwischen den Gruppen zu erkennen.Gruppenunterschiede bei der primären (FAS gesamt: F1, 58 = 14,356; p < 0.001) sowie der sekundären Zielgröße (ORIDL: F1, 58 = 210,986; p < 0.001) nach 3 Monaten sprachen für die IHM gegenüber Placebo. Lycopodium clavatum (11.7%), sulfur (11.7%), Arsenicum album (10%) und Thuja occidentalis (10%) waren die am häufigsten indizierten Mittel. In beiden Gruppen wurden keine Schädigungen, unbeabsichtigten Wirkungen, homöopathischen Verschlechterungen oder jegliche schwerwiegenden unerwünschten Ereignisse beobachtet.Die IHM erzielten signifikant bessere Effekte als Placebo in der Behandlung von Post-COVID-Ermüdung bei Erwachsenen. Definitive, belastbare Studien können eingeleitet werden, um diese Befunde zu bestätigen.

In Silico Identification of Potential Natural Product Inhibitors of Human Proteases Key to SARS-CoV-2 Infection.

Presently, there are no approved drugs or vaccines to treat COVID-19, which has spread to over 200 countries and at the time of writing was responsible for over 650,000 deaths worldwide. Recent studies have shown that two human proteases, TMPRSS2 and cathepsin L, play a key role in host cell entry of SARS-CoV-2. Importantly, inhibitors of these proteases were shown to block SARS-CoV-2 infection. Here, we perform virtual screening of 14,011 phytochemicals produced by Indian medicinal plants to identify natural product inhibitors of TMPRSS2 and cathepsin L. AutoDock Vina was used to perform molecular docking of phytochemicals against TMPRSS2 and cathepsin L. Potential phytochemical inhibitors were filtered by comparing their docked binding energies with those of known inhibitors of TMPRSS2 and cathepsin L. Further, the ligand binding site residues and non-covalent interactions between protein and ligand were used as an additional filter to identify phytochemical inhibitors that either bind to or form interactions with residues important for the specificity of the target proteases. This led to the identification of 96 inhibitors of TMPRSS2 and 9 inhibitors of cathepsin L among phytochemicals of Indian medicinal plants. Further, we have performed molecular dynamics (MD) simulations to analyze the stability of the protein-ligand complexes for the three top inhibitors of TMPRSS2 namely, qingdainone, edgeworoside C and adlumidine, and of cathepsin L namely, ararobinol, (+)-oxoturkiyenine and 3α,17α-cinchophylline. Interestingly, several herbal sources of identified phytochemical inhibitors have antiviral or anti-inflammatory use in traditional medicine. Further in vitro and in vivo testing is needed before clinical trials of the promising phytochemical inhibitors identified here.

The Prodigious Hydrogen Bonds with Sulfur and Selenium in Molecular Assemblies, Structural Biology, and Functional Materials.

Hydrogen bonds (H-bonds) play important roles in imparting functionality to the basic molecules of life by stabilizing their structures and directing their interactions. Numerous studies have been devoted to understanding H-bonds involving highly electronegative atoms like nitrogen, oxygen, and halogens and consequences of those H-bonds in chemical reactions, catalysis, and structure and function of biomolecules; but the involvement of less electronegative atoms like sulfur and selenium in H-bond formation establishes the concept of noncanonical H-bonds. Initially belittled for the "weak" nature of their interactions, these perceptions have gradually evolved over time through dedicated efforts by several research groups. This has been facilitated by advancements in experimental methods for their detection through gas-phase laser spectroscopy and solution NMR spectroscopy, as well as through theoretical predictions from high level quantum chemical calculations.In this Account, we present insights into the versatility of the sulfur and selenium centered H-bonds (S/SeCHBs) by highlighting their multifarious applications in various fields from chemical reactions to optoelectronic properties to structural biology. Our group has highlighted the significance and strength of such H-bonds in natural and modified biomolecules. Here, we have reviewed several molecular assemblies, biomolecules, and functional materials, where the role of these H-bonds is pivotal in influencing biological functions. It is worth mentioning here that the precise experimental data obtained from gas-phase laser spectroscopy have contributed considerably to changing the existing perceptions toward S/SeCHBs. Thus, molecular beam experiments, though difficult to perform on smaller model thio- or seleno-substituted Molecules, etc. (amides, nucleobases, drug molecules), are inevitable to gather elementary knowledge and convincing concepts on S/SeCHBs that can be extended from a small four-atom sulfanyl dimer to a large 14 kDa iron-sulfur protein, ferredoxin. These H-bonds can also tailor a fascinating array of molecular frameworks and design supramolecular assemblies by inter- and intralinking of individual "molecular Lego-like" units.The discussion is indeed intriguing when it turns to the usage of S/SeCHBs in facile synthetic strategies like tuning regioselectivity in reactions, as well as invoking phenomena like dual phosphorescence and chemiluminescence. This is in addition to our investigations of the dispersive nature of the hydrogen bond between metal hydrides and sulfur or selenium as acceptor, which we anticipate would lead to progress in the areas of proton and hydride transfer, as well as force-field design. This Account demonstrates how ease of fabrication, enhanced efficiency, and alteration of physicochemical properties of several functional materials is facilitated owing to the presence of S/SeCHBs. Our efforts have been instrumental in the evaluation of various S/SeCHBs in flue gas capture, as well as design of organic energy harvesting materials, where dipole moment and polarizability have important roles to play. We hope this Account invokes newer perspectives with regard to how H-bonds with sulfur and selenium can be adequately adopted for crystal engineering, for more photo- and biophysical studies with different spectroscopic methods, and for developing next-generation field-effect transistors, batteries, superconductors, and organic thin-film transistors, among many other multifunctional materials for the future.