Publications ISA – related to COronaVIrus Disease 19 (COVID-19)



2023, Rassegna della letteratura scientifica in rivista (Literature review), ENG

Food Plant Secondary Metabolites Antiviral Activity and Their Possible Roles in SARS-CoV-2 Treatment: An Overview

Giordano, Deborah; Facchiano, Angelo; Carbone, Virginia

Natural products and plant extracts exhibit many biological activities, including that related to the defense mechanisms against parasites. Many studies have investigated the biological functions of secondary metabolites and reported evidence of antiviral activities. The pandemic emergencies have further increased the interest in finding antiviral agents, and efforts are oriented to investigate possible activities of secondary plant metabolites against human viruses and their potential application in treating or preventing SARS-CoV-2 infection. In this review, we performed a comprehensive analysis of studies through in silico and in vitro investigations, also including in vivo applications and clinical trials, to evaluate the state of knowledge on the antiviral activities of secondary metabolites against human viruses and their potential application in treating or preventing SARS-CoV-2 infection, with a particular focus on natural compounds present in food plants. Although some of the food plant secondary metabolites seem to be useful in the prevention and as a possible therapeutic management against SARS-CoV-2, up to now, no molecules can be used as a potential treatment for COVID-19; however, more research is needed.

Molecules (Basel, Online) 28 (6)

DOI: 10.3390/molecules28062470


2022, Articolo in rivista, ENG

In Silico Analysis of the Effects of Omicron Spike Amino Acid Changes on the Interactions with Human Proteins

Nancy D’Arminio, Deborah Giordano, Bernardina Scafuri, Carmen Biancaniello, Mauro Petrillo, Angelo Facchiano, and Anna Marabotti

The SARS-CoV-2 variant Omicron is characterized, among others, by more than 30 amino acid changes occurring on the spike glycoprotein with respect to the original SARS-CoV-2 spike protein. We report a comprehensive analysis of the effects of the Omicron spike amino acid changes in the interaction with human antibodies, obtained by modeling them into selected publicly available resolved 3D structures of spike-antibody complexes and investigating the effects of these mutations at structural level. We predict that the interactions of Omicron spike with human antibodies can be either negatively or positively affected by amino acid changes, with a predicted total loss of interactions only in a few complexes. Moreover, our analysis applied also to the spike-ACE2 interaction predicts that these amino acid changes may increase Omicron transmissibility. Our approach can be used to better understand SARS-CoV-2 transmissibility, detectability, and epidemiology and represents a model to be adopted also in the case of other variants.


Molecules (Basel, Online) 27 (15)

DOI: 10.3390/molecules27154827

A critical evaluation of risk to reward ratio of quercetin supplementation for COVID-19 and associated comorbid conditions

Pawar A.; Russo M.; Rani I.; Goswami K.; Russo G.L.; Pal A.

The interim results of the large, multinational trials on coronavirus disease 2019 (COVID-19) using a combination of antiviral drugs appear to have little to no effect on the 28-day mortality or the in-hospital course. Therefore, there is a still vivid interest in finding alternate re-purposed drugs and nutrition supplements, which can halt or slow the disease severity. We review here the multiple preclinical studies, partially supported by clinical evidence showing the quercetin’s possible therapeutic/prophylaxis efficacy against severe acute respiratory syndrome coronavirus (SARS-CoV) as well as comorbidities like chronic obstructive pulmonary disease (COPD), diabetes mellitus, obesity, coagulopathy, and hypertension. Currently, 14 interventional clinical trials are underway assessing the efficacy of quercetin along with other antiviral drugs/nutritional supplements as prophylaxis/treatment option against COVID-19. The present review is tempting to suggest that, based on circumstantial scientific evidence and preliminary clinical data, the flavonoid quercetin can ameliorate COVID-19 infection and symptoms acting in concert on two parallel and independent paths: inhibiting key factors responsible for SARS-CoV-2 infections and mitigating the clinical manifestations of the disease in patients with comorbid conditions. Despite the broad therapeutic properties of quercetin, further high power randomized clinical trials are needed to firmly establish its clinical efficacy against COVID-19.


PTR. Phytotherapy research 36, pp. 2394–2415

DOI: 10.1002/ptr.7461

Food Involvement, Food Choices, and Bioactive Compounds Consumption Correlation during COVID-19 Pandemic: How Food Engagement Influences Consumers’ Food Habits

Chiara Medoro, Marta Cianciabella, Massimiliano Magli, Giulia Maria Daniele, Nico Lippi, Edoardo Gatti, Roberto Volpe, Vincenzo Longo, Filomena Nazzaro, Silvia Mattoni, Federica Tenaglia and Stefano Predieri

The containment measures due to the COVID-19 pandemic affected food-related activities, influencing dietary behavior, food habits, and dietary choices. This study aimed to compare the relationship between food involvement and dietary choices before and during the pandemic, investigating the role played by food in dietary habits. Responses given by 2773 Italian consumers to an online survey were studied through the Food Involvement Scale (FIS) and correlated to eating habits. FIS scores were then used to explain the importance given to food in circumstances related to well-being, health, and protection against COVID-19 and used to study the relationship between FIS and bioactive compound knowledge, use, and efficacy against COVID-19. The consumers more involved in food issues recognized the importance of food in circumstances related to well-being, health, and protection against COVID-19 and improved their diet during the pandemic. Moreover, consumers who gave more importance to food also revealed higher attention to the use of healthy substances, such as bioactive compounds, considering them effective against COVID-19. These results showed that food experiencing and involvement could be important elements to promote healthy dietary habits that are essential to maintain physical and mental health during emergency periods such as the COVID-19 pandemic.

Nutrients Nutrients 2022, 14, 1490 (14-1490), pp. 1–19

DOI: 10.3390/nu14071490


2022, Articolo in rivista, ENG

Molecular Aspects of Spike-ACE2 Interaction

Luigi De Masi (1, *); Maria Antonia Argenio (2); Deborah Giordano (2); Angelo Facchiano (2, *)

A new betacoronavirus (CoV-2) is responsible for the pandemic of severe acute respiratory syndrome (SARS) that began in China at the end of 2019, today known as COronaVIrus Disease 2019 (COVID-19). Subsequent studies confirmed the human angiotensin-converting enzyme 2 (hACE2) as the main cell receptor of spike trimeric glycoprotein, located on the viral envelope, mediating the CoV-2 invasion into the host cells through the receptor-binding domain (RBD) of the spike. Computational analysis of the known experimental 3D structures of spike-ACE2 complexes evidenced distinguishing features in the molecular interactions at the RBD-cell receptor binding interface between CoV-2 and previous CoV-1. The spike represents a key target for drug design as well as an optimal antigen for RNA/viral vector vaccines and monoclonal antibodies in order to maximize prevention and therapy of COVID-19.

Encyclopedia (Basel. 2021) 2 (1), pp. 96–108

DOI: 10.3390/encyclopedia2010007


2021, Articolo in rivista, ENG

Structural Dissection of Viral Spike-Protein Binding of SARS-CoV-2 and SARS-CoV-1 to the Human Angiotensin-Converting Enzyme 2 (ACE2) as Cellular Receptor

Deborah Giordano, Luigi De Masi, Maria Antonia Argenio, and Angelo Facchiano

An outbreak by a new severe acute respiratory syndrome betacoronavirus (SARS-CoV-2) has spread CoronaVirus Disease 2019 (COVID-19) all over the world. Immediately, following studies have confirmed the human Angiotensin-Converting Enzyme 2 (ACE2) as a cellular receptor of viral Spike-Protein (Sp) that mediates the CoV-2 invasion into the pulmonary host cells. Here, we compared the molecular interactions of the viral Sp from previous SARS-CoV-1 of 2002 and SARS-CoV-2 with the host ACE2 protein by in silico analysis of the available experimental structures of Sp-ACE2 complexes. The K417 amino acid residue, located in the region of Sp Receptor-Binding Domain (RBD) of the new coronavirus SARS-CoV-2, showed to have a key role for the binding to the ACE2 N-terminal region. The R426 residue of SARS-CoV-1 Sp-RBD also plays a key role, although by interacting with the central region of the ACE2 sequence. Therefore, our study evidenced peculiarities in the interactions of the two Sp-ACE2 complexes. Our outcomes were consistent with previously reported mutagenesis studies on SARS-CoV-1 and support the idea that a new and different RBD was acquired by SARS-CoV-2. These results have interesting implications and suggest further investigations

Biomedicines 9 (8)

DOI: 10.3390/biomedicines9081038


2020, Articolo in rivista, ENG

An investigation into the molecular basis of cancer comorbidities in coronavirus infection

Facchiano, Antonio; Facchiano, Francesco; Facchiano, Angelo

Comorbidities in COVID-19 patients often worsen clinical conditions and may represent death predictors. Here, the expression of five genes, known to encode coronavirus receptors/interactors (ACE2,TMPRSS2,CLEC4M,DPP4andTMPRSS11D), was investigated in normal and cancer tissues, and their molecular relationships with clinical comorbidities were investigated. Using expression data from GENT2 databases, we evaluated gene expression in all anatomical districts from 32 normal tissues in 3902 individuals. Functional relationships with body districts were analyzed bychilibot. We performed DisGeNet,genemaniaand DAVID analyses to identify human diseases associated with these genes. Transcriptomic expression levels were then analyzed in 31 cancer types and healthy controls from approximately 43 000 individuals, using GEPIA2 and GENT2 databases. By performing receiver operating characteristic analysis, the area under the curve (AUC) was used to discriminate healthy from cancer patients. Coronavirus receptors were found to be expressed in several body districts. Moreover, the five genes were found to associate with acute respiratory syndrome, diabetes, cardiovascular diseases and cancer (i.e. the most frequent COVID-19 comorbidities). Their expression levels were found to be significantly altered in cancer types, including colon, kidney, liver, testis, thyroid and skin cancers (P < 0.0001); AUC > 0.80 suggests that TMPRSS2, CLEC4M and DPP4 are relevant markers of kidney, liver, and thyroid cancer, respectively. The five coronavirus receptors are related to all main COVID-19 comorbidities and three show significantly different expression in cancer versus control tissues. Further investigation into their role may help in monitoring other comorbidities, as well as for follow-up of patients who have recovered from SARS-CoV-2 infection.

FEBS openbio 10 (11), pp. 2363–2374

DOI: 10.1002/2211-5463.12984



2020, Articolo in rivista, ENG

A review on drug repurposing applicable to COVID-19.

Dotolo S, Marabotti A, Facchiano A, Tagliaferri R.

Drug repurposing involves the identification of new applications for existing drugs at a lower cost and in a shorter time. There are different computational drug-repurposing strategies and some of these approaches have been applied to the coronavirus disease 2019 (COVID-19) pandemic. Computational drug-repositioning approaches applied to COVID-19 can be broadly categorized into (i) network-based models, (ii) structure-based approaches and (iii) artificial intelligence (AI) approaches. Network-based approaches are divided into two categories: network-based clustering approaches and network-based propagation approaches. Both of them allowed to annotate some important patterns, to identify proteins that are functionally associated with COVID-19 and to discover novel drug-disease or drug-target relationships useful for new therapies. Structure-based approaches allowed to identify small chemical compounds able to bind macromolecular targets to evaluate how a chemical compound can interact with the biological counterpart, trying to find new applications for existing drugs. AI-based networks appear, at the moment, less relevant since they need more data for their application.

Briefings in bioinformatics (Online)

DOI: 10.1093/bib/bbaa288



2020, Articolo in rivista, CPE

Reply to Jakovac: About COVID-19 and vitamin D

Facchiano, Angelo; Facchiano, Antonio; Bartoli, Manuela; Ricci, Alberto; Facchiano, Francesco

No abstract available

American journal of physiology: endocrinology and metabolism 318 (6), pp. E838–E838

DOI: 10.1152/ajpendo.00185.2020


2020, Rassegna della letteratura scientifica in rivista (Literature review), ENG
Covid-19 and cardiovascular risk: Susceptibility to infection to SARS-CoV-2, severity and prognosis of Covid-19 and blockade of the renin-angiotensin-aldosterone system.
An evidence-based viewpoint

Cappuccio, Francesco P.; Siani, Alfonso

The presence of cardiovascular co-morbidities and the known effects of coronaviruses on the cardiovascular system have called attention to the potential implications for patients with cardiovascular risk factors. This evidence-based viewpoint will address two questions: (a) are individuals with underlying cardiovascular risk factors (e.g. high blood pressure or diabetes) or overt disease (e.g. coronary heart disease, heart failure, kidney disease) more likely to develop severe Covid-19 and to die than those without underlying conditions? (b) does the regular use of angiotensin-converting enzyme inhibitors (ACE-i) or angiotensin-receptor blockers (ARB) make patients more likely to get infected and to die of Covid-19? With a necessary cautionary note that the evidence around the links between Covid-19 and cardiovascular disease is accruing at a fast pace, to date we can conclude that: (a) the greater susceptibility of individuals with underlying cardiovascular conditions to develop more severe Covid-19 with higher mortality rate is likely to be confounded, in part, by age and the type of co-morbidities. Patients with heart failure or chronic kidney disease might show an excess risk; (b) neither ACE-i nor ARB are associated with greater risk of SARS-Cov2 infection, or severity or risk of death in patients with Covid-19. Patients on these drugs should not stop them, unless under strict medical supervision and with the addition of a suitable replacement medicine.

NMCD. Nutrition Metabolism and Cardiovascular Diseases (Testo stamp.) 30 (8), pp. 1227–1235

DOI: 10.1016/j.numecd.2020.05.013


2020, Articolo in rivista, ENG

Roles of flavonoids against coronavirus infection

Russo M.; Moccia S.; Spagnuolo C.; Tedesco I.; Russo G.L.

In terms of public health, the 21st century has been characterized by coronavirus pandemics: in 2002-03 the virus SARS-CoV caused SARS; in 2012 MERS-CoV emerged and in 2019 a new human betacoronavirus strain, called SARS-CoV-2, caused the unprecedented COVID-19 outbreak. During the course of the current epidemic, medical challenges to save lives and scientific research aimed to reveal the genetic evolution and the biochemistry of the vital cycle of the new pathogen could lead to new preventive and therapeutic strategies against SARS-CoV-2. Up to now, there is no cure for COVID-19 and waiting for an efficacious vaccine, the development of “savage” protocols, based on “old” anti-inflammatory and anti-viral drugs represents a valid and alternative therapeutic approach. As an alternative or additional therapeutic/preventive option, different in silico and in vitro studies demonstrated that small natural molecules, belonging to polyphenol family, can interfere with various stages of coronavirus entry and replication cycle. Here, we reviewed the capacity of well-known (e.g. quercetin, baicalin, luteolin, hesperetin, gallocatechin gallate, epigallocatechin gallate) and uncommon (e.g. scutellarein, amentoflavone, papyriflavonol A) flavonoids, secondary metabolites widely present in plant tissues with antioxidant and anti-microbial functions, to inhibit key proteins involved in coronavirus infective cycle, such as PL, 3CL, NTPase/helicase. Due to their pleiotropic activities and lack of systemic toxicity, flavonoids and their derivative may represent target compounds to be tested in future clinical trials to enrich the drug arsenal against coronavirus infections.

Chemico-biological interactions (Print) 328

DOI: 10.1016/j.cbi.2020.109211


2021, Abstract in atti di convegno, ENG

Computational study of the molecular interactions in the binding of coronavirus Spike-proteins with the human Angiotensin-Converting Enzyme 2 (ACE2) cellular receptor

Deborah Giordano; Maria Antonia Argenio; Luigi De Masi; Angelo Facchiano

Due to the pandemic urgency of COVID-19, we investigated the molecular interaction of the Spike-proteins (Sp) from SARS-CoV and SARS-CoV-2 with the human Angiotensin-Converting Enzyme 2 (ACE2), recognized as the most relevant cellular receptor involved in both the coronavirus infections. SARS-CoV-2 Sp consists of a long sequence of 1273 amino acids, and the interaction with ACE2 receptor is due to its region 318-510, named Receptor-Binding Domain (RBD). On the other side, ACE2 consists of 805 amino acids and its physiological activity as peptidase regulates cardiovascular homeostasis. The interaction between ACE2 and Sp-RBD is described at atomic level by different crystallographic complexes obtained under different conditions, and available in the RCSB PDB Protein DataBank. We in silico analyzed the structural features of the Sp-ACE2 complexes and observed the surface interactions occurring in the different complex structures. The results of the comparative analysis highlight the details of the most peculiar interactions and the corresponding amino acids involved.

WebPro Proteins on the Web 2021, online,, 20-21/05/2021


2021, Abstract in atti di convegno, ENG

Molecular dissection of the inter-chain interface of the human Angiotensin-Converting Enzyme 2 (ACE2) receptor with the SARS-CoV-2 Spike-protein

Deborah Giordano (1); Maria Antonia Argenio (1); Luigi De Masi (2); Angelo Facchiano (1)

Motivation The COVID-19 pandemic has prompted many researchers to deepen knowledge of the interaction mechanisms that allow the coronavirus attack to the human target cells. It is well recognized that human ACE2 acts as a cellular receptor of the Spike-protein (Sp) characterizing the virus surface, as for the past coronavirus epidemics. The molecular interactions with Sp are of crucial importance for the successful coronavirus attack, and their complete understanding can be useful for the definition of the mechanism of action as well as for ascertaining possible interaction differences in the case of ACE2 or Sp variants. Methods We in silico analyzed the structural features of the chain interface in ACE2/SARS-CoV-2 Sp complexes, described at atomic level by different crystallographic structures available in the RCSB PDB. We observed the surface interactions by PyMol v1.3, PDBePISA and COCOMAPS, and investigated at visual level the molecular interactions by DiscoveryStudio v20.1.0. Results The results of the structural analysis on the crystallographic complexes of ACE2/SARS-CoV-2 Sp defined what amino acid residues interact with the chain-chain interface. Their physiological roles and structural features were investigated in detail and will be presented together with a comparative analysis that evidenced differences between the interaction of ACE2 with Sp of SARS-CoV-2 and SARS-CoV (previously characterized), with potential implications on the different health impact of the most recent coronavirus.

BITS 2021 Annual Meeting of the Bioinformatics Italian Society, online, 1-2/07/2021