This work aimed at evaluating the inhibitory effect of ten natural bioactive compounds (1-10) as potential inhibitors of SARS-CoV-2-3CL main protease (PDB ID: 6LU7) and SARS-CoV main proteases (PDB IDs: 2GTB and 3TNT) by molecular docking analysis. The inhibitory effect of all studied compounds was studied with compared to some proposed antiviral drugs which currently used in COVID-19 treatment such as chloroquine, hydroxychloroquine, azithromycin, remdesivir, baloxvir, lopinavir, and favipiravir. Homology modeling and sequence alignment was computed to evaluate the similarity between the SARS-CoV-2-3CL main protease and other SARS-CoV receptors. ADMET properties of all studied compounds were computed and reported. Also, molecular dynamic (MD) simulation was performed on the compound which has the highest binding affinity inside 6LU7 obtained from molecular docking analysis to study it is stability inside receptor in explicit water solvent. Based on molecular docking analysis, we found that caulerpin has the highest binding affinity inside all studied receptors compared to other bioactive compounds and studied drugs. Our homology modeling and sequence alignment showed that SARS-CoV main protease (PDB ID: 3TNT) shares high similarity with 3CLpro (96.00%). Also, ADMET properties confirmed that caulerpin obeys Lipinski's rule and passes ADMET property, which make it a promising compound to act as a new safe natural drug against SARS-CoV-2-3CL main protease. Finally, MD simulation confirmed that the complex formed between caulerpin and 3CLpro is stable in water explicit and had no major effect on the flexibility of the protein throughout the simulations and provided a suitable basis for our study. Also, binding free energy between caulerpin and 6LU7 confirmed the efficacy of the caulerpin molecule against SARS-CoV-2 main protease. So, this study suggested that caulerpin could be used as a potential candidate in COVID-19 treatment.

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Presently, the SARS-CoV-2 (COVID-19) pandemic has been spreading throughout the world. Some drugs such as lopinavir, simeprevir, hydroxychloroquine, chloroquine, and amprenavir have been recommended for COVID-19 treatment by some researchers, but these drugs were not effective enough against this virus. This study based on in silico approaches was aimed to increase the anti-COVID-19 activities of these drugs by using caulerpin and its derivatives as an adjunct drug against SARS-CoV-2 receptor proteins: the SARS-CoV-2 main protease and the SARS-CoV-2 spike protein. Caulerpin exhibited antiviral activities against chikungunya virus and herpes simplex virus type 1. Caulerpin and some of its derivatives showed inhibitory activity against Alzheimer’s disease. The web server ANCHOR revealed higher protein stability for the two receptors with disordered score (< 0.6). Molecular docking analysis showed that the binding energies of most of the caulerpin derivatives were higher than all the suggested drugs for the two receptors. Also, we deduced that inserting NH 2 , halogen, and vinyl groups can increase the binding affinity of caulerpin toward 6VYB and 6LU7, while inserting an alkyl group decreases the binding affinity of caulerpin toward 6VYB and 6LU7. So, we can modify the inhibitory effect of caulerpin against 6VYB and 6LU7 by inserting NH 2 , halogen, and vinyl groups. Based on the protein disordered results, the SARS-CoV-2 main protease and SARS-CoV-2 spike protein domain are highly stable proteins, so it is quite difficult to unstabilize their integrity by using individual drugs. Also, molecular dynamics (MD) simulation indicates that binding of the combination therapy of simeprevir and the candidate studied compounds to the receptors was stable and had no major effect on the flexibility of the protein throughout the simulations and provided a suitable basis for our study. So, this study suggested that caulerpin and its derivatives could be used as a combination therapy along with lopinavir, simeprevir, hydroxychloroquine, chloroquine, and amprenavir for disrupting the stability of SARS-CoV2 receptor proteins to increase the antiviral activity of these drugs.

Recently, a great attention has been given for applying a low-cost and effective adsorbents instead of expensive and dangerous chemical materials as a promising approach to treat wastewater. In this work, residue powder of brown macroalga Padina gymnospora (RPG), after extracting most of its active components by 70% methanol, was used as an adsorbent material for wastewater treatment. This work also reduces the costs of residue disposal. The adsorption ability of RPG is studied for removing Cd 2+ and Cr 3+ from wastewater. We investigated metal adsorption isotherms and kinetics, the effect of initial metal concentration, contact time, adsorbent dosage, temperature, pH and the RPG reusability on metal ions removal. The results showed that the removal % generally increases with decreasing concentration of metal ions. RPG has higher metal removal percentages reaching 96.2% and 78.8% for Cd 2+ and Cr 3+ , respectively, with a maxiumum adsorption capacity of 96.46 and 31.52 mg/g for Cd 2+ and Cr 3+ ,respectively at pH 6.2, 50 mg, 25 °C and initial metal concentration of 100 mg/L. The metal ions removal % increased by increasing the dosage of adsorbent and it decreased after a certain limit. The metal removal % slightly changes with increasing temperature for Cd 2+ and decreased at high-temperature for Cr 3+ . The adsorption increased with increasing pH value from 3 to 5, and decreases at pH value of 6.2 then it increased again at pH 8. The removal % and adsorption capacity at pH 8 reaches 99.58%, 99.65%, 99.85 mg/g and 39.86 mg/g for Cd 2+ and Cr 3+ , respectively. The results also showed that RPG can be reused several times for metal ions removal. In addition, Tempkin isotherms and pseudo-second-order kinetic fit the adsorption of Cd 2+ and Cr 3+ well.

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