Coronavirus disease 2019 (COVID-19) is an infectious disease with approximately 517 million confirmed cases, with the average number of cases revealing that patients recover immediately without hospitalization. However, several other cases found that patients still experience various symptoms after 3–12 weeks, which is known as a long COVID syndrome. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can activate nuclear factor kappa beta (NF-κβ) and unbind the nuclear factor erythroid 2-related factor 2 (Nrf2) with Kelch-like ECH-associated protein 1 (Keap1), causing inhibition of Nrf2, which has an important role in antioxidant response and redox homeostasis. Disrupting the Keap1–Nrf2 pathway enhances Nrf2 activity, and has been identified as a vital approach for the prevention of oxidative stress and inflammation. Hence, natural antioxidants from various sources have been identified as a promising strategy to prevent oxidative stress, which plays a role in reducing the long COVID-19 symptoms. Oxygen-rich natural antioxidant compounds provide an effective Nrf2 activation effect that interact with the conserved amino acid residues in the Keap1-binding pocket, such as Ser602, Ser363, Ser508, and Ser555. In this review, the benefits of various natural antioxidant compounds that can modulate the Nrf2 signaling pathway, which is critical in reducing and curing long COVID-19, are highlighted and discussed.
Depresi merupakan penyakit yang mempengaruhi perasaan, cara berpikir, dan tindakan. Depresi menyebabkan perasaan sedih dan / hilangnya minat pada suatu aktivitas. Depresi dapat diobati menggunakan antidepresan. Piper nigrum L. atau Lada Hitam merupakan tanaman yang dapat digunakan sebagai antidepresan. Pada lada hitam terkandung senyawa metabolit sekunder yang dapat sebagai antidepresan dengan mekanisme terhadap 5-HT1B. Penelitian ini bertujuan untuk mempelajari interaksi antara senyawa yang terkandung pada lada hitam yang berpotensi sebagai antidepresan terhadap protein 5-HT1B menggunakan metode molecular docking secara in silico. Pengujian dilakukan menggunakan aplikasi Autodock 4.2 untuk simulasi penambatan molekuler, divisualisasi dengan Biovia Discovery Studio 2020 Client, dan analisis hasil farmakokinetika serta toksisitas dari senyawa melalui situs pre-ADMET. Hasil penambatan diperoleh senyawa piperettin memiliki potensi paling besar menjadi kandidat obat antidepresan melalui mekanisme agonis 5-HT1B dibandingkan senyawa uji lainnya karena memiliki energi ikatan sebesar -8,84 kKal/mol dengan ikatan hidrogen pada residu asam amino THR134. Berdasarkan analisis hasil prediksi, Piperettin memiliki sifat farmakokinetika dengan nilai CaCo-2 54,6793; HIA 98,050270% ; PPB 92,408768%. Hasil pre-ADMET senyawa menunjukan adanya dugaan potensi karsinogen.Kata kunci: 5-HT1B, Antidepresan, Molecular Docking, Piperettin, Piper nigrum
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