Correction to: In silico investigation of the therapeutic and prophylactic potential of medicinal substances bearing guanidine moieties against COVID-19.

[This corrects the article DOI: 10.1007/s11696-022-02528-y.].

In silico investigation of the therapeutic and prophylactic potential of medicinal substances bearing guanidine moieties against COVID-19.

The current viral pandemic, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), creates health, mental, economic, and other serious challenges that are better to say global crisis. Despite the existence of successful vaccines, the possible mutations which can lead to the born of novel and possibly more dangerous variants of the virus as well as the absence of definitive treatment for this potentially fatal multiple-organ infection in critically ill patients make us keep searching. Theoretically targeting human and viral receptors and enzymes via molecular docking and dynamics simulations can be considered a wise, rational, and efficient way to develop therapeutic agents against COVID-19. In this way, The RNA-dependent RNA polymerase (RdRP), main protease, and spike glycoprotein of SARS-CoV-2 as well as the human angiotensin-converting enzyme 2 receptor and transmembrane serine protease 2 are the most discussed and studied targets that play essential roles in the viral life and infection cycle. In the current in silico investigation, the guanidine functionality containing drugs and medicinal substances such as metformin, famotidine, neuraminidase inhibitors, antimalarial medications, anticancer drug imatinib, CGP compounds, and human serine protease inhibitor camostat were studied against the above-mentioned therapeutic targets and most of them (especially imatinib) have revealed an incredible spectrum of free docking scores and MD results. The current in silico investigation that its novel perspective of view is corroborated by the different experimental and clinical evaluations, confirms that the guanidine moiety can be considered as a missing promising pharmacophore in drug design and development approaches against SARS-CoV-2. Considering the chemical potency of this polyamine group in chemical interaction creation, the observed outcomes in this virtual screening were not surprising. On the other hand, the guanidine functional group has unique physico-chemical properties such as basicity that can make the target cells intracellular pH undesirable for the virus entry, uncoating, and cytosolic lifecycle. According to the obtained results in the current study that are interestingly confirmed by the previously reported efficacy of some the guanidine carrying drugs in COVID-19, guanidine as a potential multi-target anti-SARS-CoV-2 functional scaffold deserves further comprehensive investigations. Supplementary Information: The online version contains supplementary material available at 10.1007/s11696-022-02528-y.

Synthesis and In Silico Investigation of Isatin-Based Schiff Bases as Potential Inhibitors for Promising Targets against SARS-CoV-2.

Despite the significant development in vaccines and therapeutics cocktails, there is no specific treatment available for coronavirus disease 2019 (COVID-19), caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Targeting the main protease (Mpro) of SARS-CoV-2, which possesses a key role in producing the essential viral structural and functional proteins, can be considered an efficient way to control this potentially lethal infection. Recently, some of Michael acceptor-pharmacophore containing inhibitors have been suggested as successful suppressors of the main protease. Here, we synthesized the Isatin-based Schiff bases possessing the structural pattern of a Michael acceptor-like portion employing synthesis procedures. In silico investigation of these compounds was not limited to the main protease. We have also evaluated their possible inhibitory activity against the other identified druggable targets using homology modeling, molecular docking, and molecular dynamics simulations. Our investigations revealed that the dimethyl biguanide carrying Schiff bases of Isatin-derivatives have the best binding mode and interaction energy. The dimethyl biguanide moiety-containing compounds have formed promising interactions with the key amino acid residues Cys145 and HIS41 of Mpro with a binding free energy of -7.6 kcal/mol which was lower than the positive control compound Carmofur (-6.3 kcal/mol). It also leads to the higher affinity and the much inhibitory potential against the SARS-CoV-2 RdRp and Spike glycoproteins, human TMPRSS2, and ACE2 receptors.

Risk Factors of COVID-19 Associated Mucormycosis (CAM) in Iranian Patients: A Single-Center Retrospective Study.

BACKGROUND: COVID-19 associated mucormycosis (CAM) has been known as one of the most severe post-COVID morbidities. OBJECTIVES: To describe CAM cases, identify possible risk factors, and report outcomes of patients. METHODS: This retrospective study was performed in Amir-Alam Hospital, Tehran, Iran between February 2020 and September 2021. Patients with mucormycosis who had an active or previous diagnosis of COVID-19 have been included. RESULTS: Of 94 patients with mucormycosis, 52 (33 men and 19 women; mean age: 57.0 ± 11.82 years) were identified with an active or history of COVID-19. Rhino-orbital, rhino maxillary, rhino-orbito cerebral subtypes of mucormycosis were detected in 6 (11.5%), 18(34.6%), and 28(53.8%) patients. As a control group, 130 (69 men and 61 women; mean age: 53.10 ± 14.49 years) random RT-PCR-confirmed COVID-19 patients without mucormycosis have been included. The mean interval between COVID-19 diagnosis and initial mucormycosis symptoms was 16.63 ± 8.4 days (range 0-51). Those in the CAM group had a significantly more severe course of COVID-19 (OR = 3.60, P-value < 0.01). Known history of previous diabetes mellitus (OR = 7.37, P-value < 0.01), smoking (OR = 4.55, P-value < 0.01), and history of receiving high-dose corticosteroid pulse therapy because of more severe COVID-19 (P-value = 0.022) were found as risk factors. New-onset post-COVID hyperglycemia was lower in the CAM group (46.2% vs. 63.8%; OR = 0.485, P-value = 0.028). After treatment of the CAM group, 41(78.8%) of patients recovered from mucormycosis. The mean ages of the expired patients in the CAM group were significantly higher than those who recovered from mucormycosis (66.18 ± 9.56 vs. 54.56 ± 11.22 years; P < 0.01); and COVID-19 disease was more severe (P = 0.046). CONCLUSION: Either active or history of COVID-19 can cause an increase in the risk of mucormycosis development. Some of the most important risk factors are the medical history of diabetes mellitus, smoking, and high-dose corticosteroid therapy. CAM is important possible comorbidity related to COVID-19, which could make the post-COVID conditions more complicated. More research and studies with greater sample sizes among different ethnicities are needed to explore the association between COVID-19 and mucormycosis.

Supply chain resilience in the face of uncertainty: how horizontal and vertical collaboration can help?

Purpose>The COVID-19 outbreak highlights that many supply chains are exposed to unforeseen disruptions, that risks are unavoidable, and that the international nature of supply chains can seriously disrupt normal operations. Therefore, the need for Supply Chain Resilience (SCRES) is more imperative than ever. Furthermore, collaboration in supply chains may have benefitted the response to the COVID-19 outbreak. The aim of this research is to gain a deeper understanding of how collaboration with both types of horizontal and vertical collaboration in the supply chain affects its resilience.Design/methodology/approach>A thematic analysis of the literature is used to investigate the concepts of both vertical and horizontal collaboration and supply chain resilience separately, then integrating identified themes to understand the relationship between them through a thematic map.Findings>The thematic analysis indicates that the more firms collaborate in the supply chain, the more resilient they will be. Furthermore, both horizontal and vertical collaboration between supply chain partners will enhance resilience. This relationship is positively moderated by governance in the partnership and negatively moderated by competition in the partnership.Originality/value>This is one of the first papers to provide in-depth insights into how collaboration, with both types of horizontal and vertical collaboration, affects supply chain resilience. Neither of previous articles provide an understanding of how both types of collaboration enables supply chain resilience.

Supply Chains’ Failure in Workers’ Rights with Regards to the SDG Compass: A Doughnut Theory Perspective

Many supply chains have pledged to prevent the violation of workers’ rights as part of social sustainability in their far-flung supply chains. This paper provides a way to understand why supply chains fail to overcome the violation of workers’ rights by mapping the UN SDGs onto the social foundations of the doughnut model, with respect to workers’ rights in supply chains. We develop the sustainable supply chain doughnut model with regards to the SDGs, through which we investigate workers’ rights violations. Examples from both UK-based and world-wide supply chains illustrates our conceptual model. Supply chains have shortfalls in all aspects of the social foundation when it comes to workers as one of their main stakeholders. Until supply chains are successful in overcoming shortfalls across all elements of the social foundation, moving to the next layer of the doughnut framework is impossible, which is the safe and just space for all humans, including workers. This ‘safe and just space’ seems out of reach despite international efforts such as the SDGs. The resulting conceptual model can be the foundation for descriptive, instrumental, and normative research on workers’ rights in the supply chain as part of the social sustainability.

Molecular docking and dynamics studies of Nicotinamide Riboside as a potential multi-target nutraceutical against SARS-CoV-2 entry, replication, and transcription: A new insight.

The highly contagious Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which is a newborn infectious member of the dangerous beta-coronaviruses (ß-CoVs) following SARS and MERS-CoVs, can be regarded as the most significant issue afflicting the whole world shortly after December 2019. Considering CoVs as RNA viruses with a single-stranded RNA genome (+ssRNA), the critical viral enzyme RNA dependent RNA polymerase (RdRp) is a promising therapeutic target for the potentially fatal infection COVID-19. Nicotinamide riboside (NR), which is a naturally occurring analogue of Niacin (vitamin B3), is expected to have therapeutic effects on COVID-19 due to its super close structural similarity to the proven RdRp inhibitors. Thus, at the first phase of the current molecular docking and dynamics simulation studies, we targeted SARS-CoV-2 RdRp. On the next phase, SARS-CoV RdRp, human Angiotensin-converting enzyme 2, Inosine-5'-monophosphate dehydrogenase, and the SARS-CoV-2 Structural Glycoproteins Spike, Nonstructural viral protein 3-Chymotrypsin-like protease, and Papain-like protease were targeted using the docking simulation to find other possible antiviral effects of NR serendipitously. In the current study, the resulted scores from molecular docking and dynamics simulations as the primary determinative factor as well as the observed reliable binding modes have demonstrated that Nicotinamide Riboside and its active metabolite NMN can target human ACE2 and IMPDH, along with the viral Spro, Mpro, PLpro, and on top of all, RdRp as a potential competitive inhibitor.

Examining the interactions scorpion venom peptides (HP1090, Meucin-13, and Meucin-18) with the receptor binding domain of the coronavirus spike protein to design a mutated therapeutic peptide.

The spike protein of SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2) interacts with the ACE2 receptor in human cells and starts the infection of COVID-19 disease. Given the importance of spike protein's interaction with ACE2 receptor, we selected some antiviral peptides of venom scorpion such as HP1090, meucin-13, and meucin-18 and performed docking and molecular docking analysis of them with the RBD domain of spike protein. The results showed that meucin-18 (FFGHLFKLATKIIPSLFQ) had better interaction with the RBD domain of spike protein than other peptides. We also designed some mutations in meucin-18 and investigated their interactions with the RBD domain. The results revealed that the A9T mutation had more effective interaction with the RBD domain than the meucin-18 and was able to inhibit spike protein's interaction with ACE2 receptor. Hence, peptide "FFGHLFKLTTKIIPSLFQ" can be considered as the potential drug for the treatment of COVID-19 disease.