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1.
Antioxidants (Basel) ; 11(8)2022 Aug 10.
Article in English | MEDLINE | ID: covidwho-1979097

ABSTRACT

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-κß) 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.

2.
Methods ; 203: 498-510, 2022 07.
Article in English | MEDLINE | ID: covidwho-1677216

ABSTRACT

For the last two years, the COVID-19 pandemic has continued to bring consternation on most of the world. According to recent WHO estimates, there have been more than 5.6 million deaths worldwide. The virus continues to evolve all over the world, thus requiring both vigilance and the necessity to find and develop a variety of therapeutic treatments, including the identification of specific antiviral drugs. Multiple studies have confirmed that SARS-CoV-2 utilizes its membrane-bound spike protein to recognize human angiotensin-converting enzyme 2 (ACE2). Thus, preventing spike-ACE2 interactions is a potentially viable strategy for COVID-19 treatment as it would block the virus from binding and entering into a host cell. This work aims to identify potential drugs using an in silico approach. Molecular docking was carried out on both approved drugs and substances previously tested in vivo. This step was followed by a more detailed analysis of selected ligands by molecular dynamics simulations to identify the best molecules that thwart the ability of the virus to interact with the ACE2 receptor. Because the SARS-CoV-2 virus evolves rapidly due to a plethora of immunocompromised hosts, the compounds were tested against five different known lineages. As a result, we could identify substances that work well on individual lineages and those showing broader efficacy. The most promising candidates among the currently used drugs were zafirlukast and simeprevir with an average binding affinity of -22 kcal/mol for spike proteins originating from various lineages. The first compound is a leukotriene receptor antagonist that is used to treat asthma, while the latter is a protease inhibitor used for hepatitis C treatment. From among the in vivo tested substances that concurrently exhibit promising free energy of binding and ADME parameters (indicating a possible oral administration) we selected the compound BDBM50136234. In conclusion, these molecules are worth exploring further by in vitro and in vivo studies against SARS-CoV-2.


Subject(s)
COVID-19 Drug Treatment , SARS-CoV-2 , Angiotensin-Converting Enzyme 2 , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Drug Repositioning , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Pandemics
3.
Dharmakarya : Jurnal Aplikasi Ipteks Untuk Masyarakat ; 10(2):167-173, 2021.
Article in Indonesian | Indonesian Research | ID: covidwho-1647108

ABSTRACT

Kegiatan Kuliah Kerja Nyata Pengabdian Pada Masyarakat (KKN-PPM) merupakan kesempatan kepada mahasiswa untuk serta berinovasi dan mengembangkan pemikiran agar dapat membantu mengatasi masalah di masyarakat. Pada periode ini KKN dilaksanakan secara daring akibat adanya kondisi khusus darurat yakni pandemi COVID-19. Tema seminar online KKN-PPM Potensi Manggis dalam Sediaan Sabun Antiseptik dan Olahan Pangan Fungsional Sebagai Upaya Pencegahan COVID-19 di Masa Adaptasi Baru. Seminar online ini dilakukan pada tanggal 25 Juli 2020 pukul 10.00 WIB hingga 12.05 WIB. Seminar dan workshop virtual ini mengedukasi perilaku hidup sehat dan bersih saat masa Pandemi COVID-19 termasuk bagaimana kebiasaan mencuci tangan dan penggunaan masker sebagai upaya menekan penularan COVID-1 serta manfaat kulit manggis sebagai antioksidan. pemaparan beragam manfaat antioksidan pada kulit manggis salah satunya sebagai pengatur berbagai aktivitas inflamasi dan memberi signaling pathways dalam sel imun terutama makrofag sehingga dapat mengoptimalkan kerja sistem imun. Peran bahan aktif Xanthones pada kulit manggis sebagai anti-bakteri anti-jamur anti-virus dan sumber antioksidan serta pengolahan produk kulit manggis menjadi fokus edukasi KKN-PPM. Kulit manggis dapat diolah menjadi sediaan antiseptik dan olahan pangan fungsional seperti pempek yoghurt dan wedang. Evaluasi kegiatan menggunakan One-Group Pretest-Posttest Design tentang PHBS dan potensi kulit manggis Berdasarkan hasil analisa data terdapat peningkatan pengetahuan tentang upaya perilaku hidup sehat sebagai pencegahan COVID-19 dan manfaat buah manggis sebesar 24.09 % dari data pra dan pasca kegiatan. kegiatan ini berkontribusi memberikan pengetahuan pada partisipan dalam mendukung penguatan sosialisasi perilaku hidup sehat saat masa COVID-19 dan manfaat kesehatan dari kulit manggis. Dari penelitian Xanthones pada kulit manggis berpotensi sebagai anti-virus yang mungkin dapat dikembangkan lebih lanjut sebagai sumber zat aktif untuk terapi COVID-19.

4.
Dharmakarya : Jurnal Aplikasi Ipteks Untuk Masyarakat ; 10(3):182-186, 2021.
Article in Indonesian | Indonesian Research | ID: covidwho-1645695

ABSTRACT

Pandemi Coronavirus yang diakibatkan oleh SARS-CoV-2 (COVID-19) telah menyebabkan berbagai permasalahan meliputi kesehatan ekonomi dan sosial. Penyesuaian dalam menjalani kehidupan sehari-hari di masa pandemi penting untuk dilakukan demi mencegah penularan dan menjaga stabilitas ekonomi masyarakat. Dalam kegiatan pengabdian kepada masyarakat Desa Sayang, Kabupaten Sumedang, dilakukan survey mengenai pengetahuan dan kesadaran masyarakat dalam masa adaptasi kebiasaan baru (AKB) dan ditindaklanjuti dengan pemberian materi berupa Sosialisasi Protokol Adaptasi Kebiasan Baru pada Masyarakat Kabupaten Sumedang dalam bentuk webinar. Hasil survei menunjukkan bahwa 95,2% masyarakat sudah mengetahui adanya penerapan protokol kesehatan di masa AKB. Namun demikian hanya 64% masyarakat saja yang mengetahui tata cara pelaksanaan protokol kesehatan di masa AKB. Dengan demikian diharapkan bahwa melalui sosialisasi protokol kesehatan di masa AKB dapat meningkatkan pengetahuan dan kesadaran masyarakat dalam menjalankan hidup sehat di masa AKB

5.
J Adv Pharm Technol Res ; 12(3): 285-290, 2021.
Article in English | MEDLINE | ID: covidwho-1323365

ABSTRACT

More than 111 million people worldwide have been affected by the COVID-19 outbreak caused by SARS-CoV-2. The main therapeutic target of COVID-19 is main protease (Mpro). It plays a key role as an enzyme in the SARS-CoV-2 replication and transcription. In this case, the alpha-mangostin potentially has antiviral activity against Mpro by inhibiting this enzyme. Nevertheless, the alpha-mangostin has low solubility and a lack of information about alpha-mangostin activity against the SARS-CoV-2. The aim of this study is to describe the molecular interactions and identify the pharmacokinetics profile between alpha-mangostin and its derivatives. in silico study was conducted by pharmacokinetics and toxicity prediction, molecular docking simulation, and Lipinski's rule of five. FKS9 has a Gibbs free energy value of-10.5 kcal/mol with an inhibition constant of 36.45 µM and an interaction with amino acid His41 residue. Its human intestinal absorption and Caco-2 values were 95.13% and 47.71% while the plasma protein binding and blood-brain barrier values were 96.66% and 6.99%. FKS9 also has no mutagenic and carcinogenic potential. FKS9 as an alpha-mangostin derivative had the best interaction with the Mpro enzyme and its pharmacokinetic profiles was identified.

6.
Majalah Farmasetika ; 5(4), 2020.
Article in Indonesian | Indonesian Research | ID: covidwho-1264873

ABSTRACT

Wabah pandemi COVID-19 merupakan peristiwa yang berdampak besar secara global dalam waktu singkat. Hampir seluruh sektor terpengaruh akibat wabah ini, salah satunya adalah sektor industri farmasi. Keberlanjutan rantai pasok perbekalan farmasi menjadi persoalan akibat pembatasan aktivitas di berbagai wilayah. Artikel mini review ini membahas dampak COVID-19 terhadap sistem rantai pasok industri farmasi dan strategi yang dapat dilakukan oleh industri farmasi di tengah masa pandemi COVID-19. Kata Kunci: COVID-19, Industri Farmasi, Rantai Pasok

7.
Molecules ; 25(17)2020 Sep 01.
Article in English | MEDLINE | ID: covidwho-742825

ABSTRACT

Over the years, coronaviruses (CoV) have posed a severe public health threat, causing an increase in mortality and morbidity rates throughout the world. The recent outbreak of a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the current Coronavirus Disease 2019 (COVID-19) pandemic that affected more than 215 countries with over 23 million cases and 800,000 deaths as of today. The situation is critical, especially with the absence of specific medicines or vaccines; hence, efforts toward the development of anti-COVID-19 medicines are being intensively undertaken. One of the potential therapeutic targets of anti-COVID-19 drugs is the angiotensin-converting enzyme 2 (ACE2). ACE2 was identified as a key functional receptor for CoV associated with COVID-19. ACE2, which is located on the surface of the host cells, binds effectively to the spike protein of CoV, thus enabling the virus to infect the epithelial cells of the host. Previous studies showed that certain flavonoids exhibit angiotensin-converting enzyme inhibition activity, which plays a crucial role in the regulation of arterial blood pressure. Thus, it is being postulated that these flavonoids might also interact with ACE2. This postulation might be of interest because these compounds also show antiviral activity in vitro. This article summarizes the natural flavonoids with potential efficacy against COVID-19 through ACE2 receptor inhibition.


Subject(s)
Angiotensin-Converting Enzyme Inhibitors/pharmacology , Antiviral Agents/pharmacology , Betacoronavirus/drug effects , Betacoronavirus/physiology , Biological Products/pharmacology , Coronavirus Infections/virology , Flavonoids/pharmacology , Pneumonia, Viral/virology , Angiotensin-Converting Enzyme 2 , Angiotensin-Converting Enzyme Inhibitors/chemistry , Antiviral Agents/chemistry , Biological Products/chemistry , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Disease Susceptibility , Flavonoids/chemistry , Humans , Life Cycle Stages , Models, Molecular , Pandemics , Peptidyl-Dipeptidase A/chemistry , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Population Surveillance , SARS-CoV-2 , Structure-Activity Relationship
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