Ferro M. et al., AJAP, 2021; 4:15 Review Article AJAP (2021) 4:15 American Journal of Anatomy and Physiology (ISSN:2637-4714) The Possible Effects of Asiatic Herbs in SARS-COV-2 and their Mechanism of Action Ferro M.*, Graubard A., Ledezma R., Escalante P., Channan G., Dotres V. and Bencomo Y. Department of Sciences, Nutrition Formulators Inc., Miramar, Fl, USA. ABSTRACT In 2019, a new virus called Severe Acute Respiratory Syndrome Keywords: SARS-COV-2; ACE2; Coronavirus 2 (SARS-CoV-2) gave rise to an unknown outbreak COVID-19; Asiatic Herbs that spread in China’s Hubei province, triggering a new epidemic known as coronavirus-19 (COVID -19). Several studies have *Correspondence to Author: demonstrated the metabolic pathways of SARS-COV-2 in angio- Marcelo Ferro tensin-converting enzyme receptors 2 (ACE2). With this, others have been considering an approach with drugs that bind to ACE2 Department of Sciences Nutrition receptors as well as antiviral activity as a possible treatment op- FormulatorsInc., 10407 N Commer- tion for the disease. Thus, the objective of this present review ce, Parkway, Miramar, Fl 33025 Mi- was to evaluate some Asiatic herbs for both the prevention and ramar, Fl, USA. treatment of COVID-19. Some herbs, such as the extract of Arte- misia annua (Artemisinins) and the extract of Isatis How to cite this article: indigotica (Emodin), showed to be effective as inhibitors of ad- Ferro M., Graubard A., Ledezma R., hesion of some viruses. Some studies observed this in the Escalante P., Channan G., Dotres V SARS-CoV S / ACE -2 protein interaction in which it inhibited the adhesion of the virus to the cell surface. Similarly, Glycyrrhiza . and Bencomo Y.. The Possible glabra extract (Licorice) showed significant inhibiting action on Effects of Asiatic Herbs in SARS- the influenza virus and was shown to be an effective antiviral in COV-2 and their Mechanism of Act- many other viruses by weakening virus activity, such as inhibiting ion.American Journal of Anatomy virus gene expression and replication, reducing adhesion force and Physiology, 2021; 4:15. and stress through the reduction of high-mobility-group box1 (HMGB1) binding to DNA. Additionally, one of the best herbs in effective concentration value (EC50) found in this study was Lycoris Radiata with EC50: 2,4 ± 0.2 μg / ml. The results pre- sented in this review are promising in the search for prophylactic eSciPub LLC, Houston, TX USA. treatment in a viral pandemic such as SARS-VOC-2. However, Website: https://escipub.com/ more clinical trials to validate the processes of the effectiveness of both plants and their extracts, as well as the synergy between the plants themselves are needed to validate future herbal treat- ments against SARS-VOC-2. AJAP: https://escipub.com/american-journal-of-anatomy-and-physiology/ 1 Ferro M. et al., AJAP, 2021; 4:15 Introduction protocols for the disease [3]. In 2019, a novel coronavirus named Severe Understanding the metabolic pathway of Acute Respiratory Syndrome Coronavirus 2 SARS-CoV (SARS-CoV-2) with unknown origin spread in the Several studies have demonstrated the Hubei province of China [1]. The epidemic metabolic pathways of SARS-COV-2 in disease caused by SARS-CoV-2, also known as angiotensin-converting enzyme receptors 2 coronavirus disease-19 (COVID-19) [2]. The (ACE2) (Fig. 1) [6, 7]. ACE2 acts as a host cell medical community understands that COVID-19 receptor for SARS-CoV [8]. Binding to ACE2 triggers an inflammatory reaction in the human stimulates clathrin-dependent endocytosis of body in response to the virus that is worse than ACE2 and SARS-CoV, which is essential for viral the virus itself [3]. This has led some people to infection to occur [7]. The ACE2 decrease in the experience severe symptoms and in cases has cell surface, causing an increase in angiotensin led to deaths [4]. Many studies are being carried II, consequently causing an activation in the out in several countries to discover antiviral angiotensin II type-1 receptor that triggers drugs to combat COVID-19 [5]. Currently, despite severe complications to the lung tissue [9]. Many the collaborative efforts of governments, studies have been considering an approach with researchers, and the pharmaceutical industry, drugs that bind to ACE2 receptors as a possible there are no substantially significant treatment treatment option [7]. Figure 1 TNF-α: Tumor Necroses Factor alfa; TNF-α R: Tumor Necroses Factor alfa receptor; AT1R: Angiotensin II type 1 receptor; ADAM17: ADAM metallopeptidase domain 17; ACE2: Angiotensin-converting enzyme 2; TMPRSS2: Transmembrane protease, serine 2; Ang II: Angiotensin II; Ang 1-7: Angiotensin 1-7. Furthermore, researchers have reported the causes COVID-19 [10]. need for urgency in understanding the Spike Protein in SARS-COV-2 pathogenesis of severe acute respiratory Clinical studies have shown that the spike syndrome produced by SARS-CoV-2, which protein SARS-CoV-2 (S) binds to ACE2 and AJAP: https://escipub.com/american-journal-of-anatomy-and-physiology/ 2 Ferro M. et al., AJAP, 2021; 4:15 together with host proteases, mainly surface unit, S1, of the protein S to a cell receptor, transmembrane serine protease 2 (TMPRSS2), which facilitates the attachment of the virus to promotes cell entry for the virus [11]. In severe the surface of the target cells [14]. In addition, acute respiratory syndrome, the spike protein is entry requires S protein priming by cellular one of the main structural proteins observed in proteases, which entails S protein cleavage at this process [12]. It is essential for the interaction the S1/S2 and the S2 site and allows fusion of of the virus with host cell receptors and viral and cellular membranes, a process driven subsequent fusion of the viral envelope with the by the S2 subunit (Fig. 2) [12, 14]. According to Li host cell membrane to allow infection [13]. The et al. (2003), SARS-S engages angiotensin- spike (S) protein of coronaviruses is one of the converting enzyme 2 (ACE2) as the entry proteins responsible for viral entry into target receptor [15]. Through this, it employs the cellular cells [12]. The adhesion and entry of the virus into serine protease TMPRSS2 for S protein priming the cells depend on the attachment of the (Fig. 2) [16]. Figure 2 S1 and S2: SARS-COV-2 Skype protein; HR1 and HR2: Heptad Repeat 1 and 2; 6-HB: Six-helix bundle Transmembrane serine protease 2 (TMPR- and macrophages [17], ACE2 expression is not SS2) limited to the lung, as extrapulmonary spread of Several studies have sought to understand how SARS-CoV has been observed in ACE2+ SARS-2-S facilitates viral entry into target cells tissues [18, 14, 19]. Although the affinity of SARS-S and how this process can be blocked. According and SARS-2-S for ACE2 has yet to be compared, to Hoffman et al. (2020), the study result the same can be expected for SARS-CoV-2 in provided evidence that the entry of SARS-CoV- relation to host cell adhesion [14]. In light of the 2 into the host cell depends on the SARS-CoV potential increase in the transmissibility of ACE2 receptor and can be blocked by a clinically SARS-CoV-2 in relation to SARS-CoV, it can be proven inhibitor of the cellular serine protease speculated that the new virus may exploit factors TMPRSS2 employed by SARS-CoV-2 for S promoting cell-binding more efficiently than protein initiation (Fig. 3) [14]. Although SARS- SARS-CoV to guarantee a robust infection of CoV2 in the lung mainly infects pneumocytes cells ACE2 + in the upper respiratory tract [14]. AJAP: https://escipub.com/american-journal-of-anatomy-and-physiology/ 3 Ferro M. et al., AJAP, 2021; 4:15 Figure 3 ACE2: Angiotensin-converting enzyme 2; TMPRSS2: Transmembrane protease, serine 2 In view of the need to test new drugs that prevent action is not available, their secondary the anion of SARS-COV-2 on the surface of the metabolites have been attracting the attention of host cell, Cheong et al. (2020) reported in their the scientific community as these metabolites studies that artemisinins derivate extract of the have to impact bioactive properties to control plant Artemisia annua could act on ACE2 viral replication [24]. receptors [20]. Several studies have reported that India is another country that depended strategies to block receptors so that SARS-COV- predominantly on herbal medicines under 2 does not adhere to ACE2 would be a great way different domain names such as Ayurveda, to control the SARS-COV-2 pandemic [21]. Siddha and Unani [21]. According to researchers, Further studies are needed to verify the possible although the advent of allopathic medicines has mechanisms of action of these plants in the decreased the prevalence of herbal treatments, metabolism of ACE2, as we can see below [20]. the current pandemic emphasizes the need to Several studies have highlighted the role of review these plants and study them using Traditional Chinese Medicine in treating patients advanced tools and approaches [25]. Innovative with SARS-CoV-2[22]. However, these compre- research is required to dissect the medicinal hensive studies are not available in countries value of plants to identify suitable with a solid background in the use of medicinal phytocomposites that can serve as possible plants for the treatment of broad-spectrum molecules in the treatment of SARS-CoV-2 [21]. diseases [21]. China has an excellent track record Following are the herbals we have identified as in using traditional plant-based formulations for having the most promising possibilities to be successfully treating SARS coronavirus (SARS- used in phyto-therapies in the treatment of CoV) in the Guangdong Province between 2002 SARS-COV and SARS-CoV-2.