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1.
researchsquare; 2022.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-1979637.v1

ABSTRACT

Background Ricinus communis L. is a medicinal plant displays valuable pharmacological properties. Diverse phytochemical constituents display valuable pharmacological properties, including antioxidant, antimicrobial, analgesic, antipyretic, antibacterial, antiviral, and anti-inflammatory property. This study targeted to isolate and identify some constituents of R. communis leaves using ultra-performance liquid chromatography coupled with mass spectroscopy (UPLC-MS/MS) and different chromatographic techniques, then characterize the potential cytotoxicity, anti-MERS-CoV and anti-SARS-CoV-2 activity in vitro. Isolated phytoconstituents and remdesivir are assessed for in-silico anti-COVID-19 activity by inhibiting the main protease and spike protein using molecular docking tools. Methods: The CH2Cl2 fraction was subjected to repeated chromatographic separation to isolate the phytochemicals, and their structures were elucidated using nuclear magnetic resonance spectroscopy. UPLC-Triple TOF-MS/MS was performed to determine the different phytochemicals in the CH2Cl2 fraction. The in vitro anti-MERS and anti-SARS-CoV2 activity for different fractions and for two pure isolated compounds, lupeol (RS) and ricinine (RS1) were evaluated using Plaque reduction assay and IC50 based on their cytotoxic concentration (CC50) from an MTT assay using Vero E6 cell line. Molecular docking studies were carried out for both SARS-CoV-2 spike (S) and main protease (Mpro) receptors then examined the possible mechanisms of action. Results: The methylene chloride extract exhibited pronounced virucidal effect with more than a 90% viral inhibitory effect, it showed activity against SARS-CoV- 2 (IC50 = 1.76µg/ml) with high safety index, SI = 291.5. It was also shown that ricinine had superior potential activity against SARS-CoV-2, (IC50 = 2.5 µg/ ml). This constituent was less effective for MERS, IC50 = 87.2 µg/ ml. Lupeol displayed the most potency against MERS, (IC50 = 5.28 µg/ ml), SI = 67.27, but was less effective for SARS, IC50 = 19.5 µg/ ml. Ricinine showed significant binding to (3CLpro) and modest affinity for (S) spike protein, along with a possible interaction with SARS-CoV-2 major protease. Ricinine appeared to be the most biologically active. Conclusion: The study showed that Ricinus communis and its isolated compounds have potential natural virucidal activity against SARS-COV-2, however, additional exploration is necessary for further chemical modification of these structures, guided by the molecular docking tools and study for their in vivo activity.


Subject(s)
COVID-19
2.
Eduan Wilkinson; Marta Giovanetti; Houriiyah Tegally; James E San; Richard Lessels; Diego Cuadros; Darren P Martin; Abdel-Rahman N Zekri; Abdoul Sangare; Abdoul Salam Ouedraogo; Abdul K Sesay; Adnene Hammami; Adrienne A Amuri; Ahmad Sayed; Ahmed Rebai; Aida Elargoubi; Alpha K Keita; Amadou A Sall; Amadou Kone; Amal Souissi; Ana V Gutierrez; Andrew Page; Arnold Lambisia; Arash Iranzadeh; Augustina Sylverken; Azeddine Ibrahimi; Bourema Kouriba; Bronwyn Kleinhans; Beatrice Dhaala; Cara Brook; Carolyn Williamson; Catherine B Pratt; Chantal G Akoua-Koffi; Charles Agoti; Collins M Moranga; James D Nokes; Daniel J Bridges; Daniel L Bugembe; Deelan Doolabh; Deogratius Ssemwanga; Derek Tshabuila; Diarra Bassirou; Dominic S.Y. Amuzu; Dominique Goedhals; Dorcas Maruapula; Edith N Ngabana; Eddy Lusamaki; Edidah Moraa; Elmostafa El Fahime; Emerald Jacob; Emmanuel Lokilo; Enatha Mukantwari; Essia Belarbi; Etienne Simon-Loriere; Etile A Anoh; Fabian Leendertz; Faida Ajili; Fares Wasfi; Faustinos T Takawira; Fawzi Derrar; Feriel Bouzid; Francisca M Muyembe; Frank Tanser; Gabriel Mbunsu; Gaetan Thilliez; Gert van Zyl; Grit Schubert; George Githinji; Gordon A Awandare; Haruka Abe; Hela H Karray; Hellen Nansumba; Hesham A Elgahzaly; Hlanai Gumbo; Ibtihel Smeti; Ikhlass B Ayed; Imed Gaaloul; Ilhem B.B. Boubaker; Inbal Gazy; Isaac Ssewanyana; Jean B Lekana-Douk; Jean-Claude C Makangara; Jean-Jacques M Tamfum; Jean M Heraud; Jeffrey G Shaffer; Jennifer Giandhari; Jingjing Li; Jiro Yasuda; Joana Q Mends; Jocelyn Kiconco; Jonathan A Edwards; John Morobe; John N Nkengasong; John Gyapong; John T Kayiwa; Jones Gyamfi; Jouali Farah; Joyce M Ngoi; Joyce Namulondo; Julia C Andeko; Julius J Lutwama; Justin O Grady; Kefenstse A Tumedi; Khadija Said; Kim Hae-Young; Kwabena O Duedu; Lahcen Belyamani; Lavanya Singh; Leonardo de O. Martins; Madisa Mine; Mahmoud el Hefnawi; Mahjoub Aouni; Maha Mastouri; Maitshwarelo I Matsheka; Malebogo Kebabonye; Manel Turki; Martin Nyaga; Matoke Damaris; Matthew Cotten; Maureen W Mburu; Maximillian Mpina; Michael R Wiley; Mohamed A Ali; Mohamed K Khalifa; Mohamed G Seadawy; Mouna Ouadghiri; Mulenga Mwenda; Mushal Allam; My V.T. Phan; Nabil Abid; Nadia Touil; Najla Kharrat; Nalia Ismael; Nedio Mabunda; Nei-yuan Hsiao; Nelson Silochi; Ngonda Saasa; Nicola Mulder; Patrice Combe; Patrick Semanda; Paul E Oluniyi; Paulo Arnaldo; Peter K Quashie; Reuben Ayivor-Djanie; Philip A Bester; Philippe Dussart; Placide K Mbala; Pontiano Kaleebu; Richard Njouom; Richmond Gorman; Robert A Kingsley; Rosina A.A. Carr; Saba Gargouri; Saber Masmoudi; Samar Kassim; Sameh Trabelsi; Sami Kammoun; Sanaa Lemriss; Sara H Agwa; Sebastien Calvignac-Spencer; Seydou Doumbia; Sheila M Madinda; Sherihane Aryeetey; Shymaa S Ahmed; Sikhulile Moyo; Simani Gaseitsiwe; Edgar Simulundu; Sonia Lekana-Douki; Soumeya Ouangraoua; Steve A Mundeke; Sumir Panji; Sureshnee Pillay; Susan Engelbrecht; Susan Nabadda; Sylvie Behillil; Sylvie van der Werf; Tarik Aanniz; Tapfumanei Mashe; Thabo Mohale; Thanh Le-Viet; Tobias Schindler; Upasana Ramphal; Magalutcheemee Ramuth; Vagner Fonseca; Vincent Enouf; Wael H Roshdy; William Ampofo; Wolfgang Preiser; Wonderful T Choga; Yaw Bediako; Yenew K. Tebeje; Yeshnee Naidoo; Zaydah de Laurent; Sofonias K Tessema; Tulio de Oliveira.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.05.12.21257080

ABSTRACT

The progression of the SARS-CoV-2 pandemic in Africa has so far been heterogeneous and the full impact is not yet well understood. Here, we describe the genomic epidemiology using a dataset of 8746 genomes from 33 African countries and two overseas territories. We show that the epidemics in most countries were initiated by importations, predominantly from Europe, which diminished following the early introduction of international travel restrictions. As the pandemic progressed, ongoing transmission in many countries and increasing mobility led to the emergence and spread within the continent of many variants of concern and interest, such as B.1.351, B.1.525, A.23.1 and C.1.1. Although distorted by low sampling numbers and blind-spots, the findings highlight that Africa must not be left behind in the global pandemic response, otherwise it could become a breeding ground for new variants.

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