A Review of Selected Phyto-derivative Compounds Evaluated by In silico studie as Potential Effective Options to Combat Life Threatening COVID-19

SARS-COV-2 identi ied as COVID-19, has become the world’s most contagious and dangerous pandemic disease today. It was irstly reported in Wuhan, China, in December 2019, then due to its strong infectious nature, it had spread to almost 214 countries. Precautionary steps remain the only mandatory technique before a successful form of treatment or vaccine is created to avoid person-to-person transmissions. In the absence of any unique or therapeutic vaccine against this virus, current attempts are being made to ind a cure for this pandemic. Using derivatives from previously known antiviral drugs are a bene icial strategy until a speci ic treatment methodology for COVID-19 is available. Since ancient times, herbal medicines have been used as natural remedies for treating different infectious diseases. A good way to treat COVID-19 will be to look for new compounds from natural sources known for their high safety and applicability since the development of innovative drugs takes a long time and cost. Molecular docking analysis is routinely used in modern drug research to understand and predict the interaction between themolecule of the drug and themicrobe’s target protein. Drugs designed in this way can prevent access of pathogens into host cells and replication. The present study gives an insight about some plant phytoderivatives that were examined via in silico studies to have the potentiality in treating coronavirus disease through various potential mechanisms such as hindering genome replication, inhibition of spike proteins or preventing in lammatory storm that causes lung injury.

COVID-19, Medicinal Plants, Phytoderivatives, In silico, Spike protein, Viral protease A SARS-COV-2 identi ied as COVID-19, has become the world's most contagious and dangerous pandemic disease today. It was irstly reported in Wuhan, China, in December 2019, then due to its strong infectious nature, it had spread to almost 214 countries. Precautionary steps remain the only mandatory technique before a successful form of treatment or vaccine is created to avoid person-to-person transmissions. In the absence of any unique or therapeutic vaccine against this virus, current attempts are being made to ind a cure for this pandemic. Using derivatives from previously known antiviral drugs are a bene icial strategy until a speci ic treatment methodology for COVID-19 is available. Since ancient times, herbal medicines have been used as natural remedies for treating different infectious diseases. A good way to treat COVID-19 will be to look for new compounds from natural sources known for their high safety and applicability since the development of innovative drugs takes a long time and cost. Molecular docking analysis is routinely used in modern drug research to understand and predict the interaction between the molecule of the drug and the microbe's target protein. Drugs designed in this way can prevent access of pathogens into host cells and replication. The present study gives an insight about some plant phytoderivatives that were examined via in silico studies to have the potentiality in treating coronavirus disease through various potential mechanisms such as hindering genome replication, inhibition of spike proteins or preventing in lammatory storm that causes lung injury.
Besides they are non-toxic and noncarcinogenic, these phytocompounds showed the desired af inity to bind at all the active sites of RNA binding domain of nucleocapsid phosphoprotein of COVID-1. Thus, they might be used to develop an effective therapy against COVID-19. (Rolta et al., 2020)  These phenolic compounds had a higher af inity on the binding sites comparing to remdesivir and hydroxychloroquine. As they do not have toxicities, these compounds can be used in In vivo or In vitro and evaluations. (Elmi et al., 2020) Continued on next page These compounds displayed high potentiality to be inhibitory agents against the viral main protease (Mpro). (Khaerunnisa et al., 2020) 38.Brazilin. 39.Hesperidin.
They had moderate to high af inity to bind with SARS-CoV-2 enzymes. Thus, they may inhibit the attachment and replication of SARS-CoV-2. (Koshak and Koshak, 2020) (Vijayakumar et al., 2020) patients with chronic diseases such as asthma, diabetes and heart problems, are more vulnerable to coronavirus disease (Rothan and Byrareddy, 2020). The outburst of coronavirus was detected irstly in Wuhan, China. On 30 January 2020, due to its rapid transmission, WHO declared COVID-19 as a public health emergency of international concern (Sohrabi et al., 2020). It has spread to over 200 countries worldwide with about 39 774 852 con irmed cases and more than 1 110 902 death cases as of October 14, 2020 (ECDC, 2020).
In addition to previously identi ied agents such as SARS-CoV and the Middle East respiratory syndrome (MERS) viruses, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is considered the causative agent for COVID-19. To attack the lower respiratory system; they invade epithelial cells of the lung then, transfer their nucleocapsid and replicate in the cytoplasm depending on the cellular machinery of the host cells.
In addition, they sometimes have effects on other parts of the body like gastrointestinal tract, central nervous system, kidney, liver and heart. SARS-CoV-2 is a member of the Coronaviridae family which has a large, enveloped single-stranded ribonucleic acid (RNA). Using its binding residues, it can interact with the Angiotensin-converting enzyme-2 directly (Cynthia and Yingzhu, 2020).
As the rapid transmission of COVID-19 may be disastrous for the whole world, certain preventive methods have been recommended by the healthcare authorities. In addition to wearing masks and regular hand washing, intensive testing, quick detection of suspected patients and quarantining of infected patients may help to counteract and control the progress of this infectious virus (Sohrabi et al., 2020).
To date, no vaccine or drug is available to overcome COVID-19. Now, the strategy used by researchers is to repurpose existing drugs. Therefore, several popular broad-spectrum antiviral drugs such as HIVprotease inhibitors and Nucleoside analogues are being evaluated against this infection to be used as a promising treatment methodology (Harapan et al., 2020).
In this study, a summary of in silico studies were performed to ind natural compounds that may be countermeasure against COVID-19.

Methodology
In the present study, search was done by keywords such as COVID-19, medicinal plants, phytoconstituents, spike protein, viral protease and in silico.
Electronic literature review method was used in this work. The databases were gathered from different databases such as Google, Science direct, PubMed, etc. Related articles were selected for review.

RESULTS
The results of in silico studies showed that phytoderivatives from different medicinal plants such as Prunus persica (L.) Batsch, Tinospora cordifolia, Rheum emodi, Nigella sativa, etc. are effective inhibitors for COVID-19. Additional information is shown in Table 1.

CONCLUSIONS
This review summarizes different in silico researches that studied the effectiveness of some phytoconstituents against the newly emerged COVID-19 infection and investigated their possible usage in drugs formulations for the treatment of this virus. Hence, the outcomes prove the values of these studies, that can result in inding new drugs based on natural compounds and emphasize them as suitable possible treatments of COVID-19 pandemic.On the other hand, caution must be taken before applying the results of in silico studies by performing appropriate in-vitro and in-vivo accurate research works.