Pyodermitis during Nivolumab Treatment for Non-Small Cell Lung Cancer: A Case Report and Review of the Literature.

Immunotherapy in oncology is replacing traditional therapies due to it specific action and limited side effects. Despite the high efficacy of immunotherapy, side effects such as bacterial infection have been reported. Bacterial skin and soft tissue infections represent one of the most important differential diagnoses in patients presenting with reddened and swollen skin and soft tissue. Among these infections, cellulitis (phlegmon) and abscesses are the most frequent. In most cases, these infections occur locally with possible contiguous spread, or as a multifocal manifestation, especially in immunocompromised patients. Herein, we report a case of pyodermitis in an immunocompromised district in a patient treated with nivolumab for non-small cell lung cancer. A 64-year-old, smoker male patient showed cutaneous lesions at a different evolution level in the left arm, all in a tattooed area, with one phlegmon and two ulcerated lesions. Microbiological cultures and gram staining revealed an infection caused by a methicillin-susceptible but erythromycin-resistant (ER-R), clindamycin-resistant (CL-R), and gentamicin-resistant (GE-R) Staphylococcus aureus strain. Despite immunotherapy becoming a milestone in oncologic treatment, more than the spectrum of immune-mediated toxicities of these agents needs to be investigated. This report highlights the importance of considering lifestyle and cutaneous background before starting immunotherapy for cancer treatment, with an emphasis on pharmacogenomics and the possibility of modified skin microbiota predisposing to cutaneous infections in patients treated with PD-1 inhibitors.

Deciphering the Broad Antimicrobial Activity of Melaleuca alternifolia Tea Tree Oil by Combining Experimental and Computational Investigations.

Tea Tree Oil (TTO) is an essential oil obtained from the distillation of Melaleuca alternifolia leaves and branches. Due to its beneficial properties, TTO is widely used as an active ingredient in antimicrobial preparations for topical use or in cosmetic products and contains about 100 different compounds, with terpinen-4-ol, γ-terpinene and 1,8-cineole (or eucalyptol) being the molecules most responsible for its biological activities. In this work, the antimicrobial activity of whole TTO and these three major components was evaluated in vitro against fungi, bacteria and viruses. Molecular dynamics simulations were carried out on a bacterial membrane model and a Coxsackievirus B4 viral capsid, to propose an atomistic explanation of their mechanism of action. The obtained results indicate that the strong antimicrobial activity of TTO is attributable to the induction of an altered membrane functionality, mediated by the incorporation of its components within the lipid bilayer, and to a possible ability of the compounds to bind and alter the structural properties of the viral capsid.

Potential Use of Tea Tree Oil as a Disinfectant Agent against Coronaviruses: A Combined Experimental and Simulation Study.

The COVID-19 pandemic has highlighted the relevance of proper disinfection procedures and renewed interest in developing novel disinfectant materials as a preventive strategy to limit SARS-CoV-2 contamination. Given its widely known antibacterial, antifungal, and antiviral properties, Melaleuca alternifolia essential oil, also named Tea tree oil (TTO), is recognized as a potential effective and safe natural disinfectant agent. In particular, the proposed antiviral activity of TTO involves the inhibition of viral entry and fusion, interfering with the structural dynamics of the membrane and with the protein envelope components. In this study, for the first time, we demonstrated the virucidal effects of TTO against the feline coronavirus (FCoVII) and the human coronavirus OC43 (HCoV-OC43), both used as surrogate models for SARS-CoV-2. Then, to atomistically uncover the possible effects exerted by TTO compounds on the outer surface of the SARS-CoV-2 virion, we performed Gaussian accelerated Molecular Dynamics simulations of a SARS-CoV-2 envelope portion, including a complete model of the Spike glycoprotein in the absence or presence of the three main TTO compounds (terpinen-4-ol, γ-terpinene, and 1,8-cineole). The obtained results allowed us to hypothesize the mechanism of action of TTO and its possible use as an anti-coronavirus disinfectant agent.

Antifungal Effect of All-trans Retinoic Acid against Aspergillus fumigatus In Vitro and in a Pulmonary Aspergillosis In Vivo Model.

Aspergillus fumigatus is the most common opportunistic fungal pathogen and causes invasive pulmonary aspergillosis (IPA), with high mortality among immunosuppressed patients. The fungistatic activity of all-trans retinoic acid (ATRA) has been recently described in vitro We evaluated the efficacy of ATRA in vivo and its potential synergistic interaction with other antifungal drugs. A rat model of IPA and in vitro experiments were performed to assess the efficacy of ATRA against Aspergillus in association with classical antifungal drugs and in silico studies used to clarify its mechanism of action. ATRA (0.5 and 1 mM) displayed a strong fungistatic activity in Aspergillus cultures, while at lower concentrations, synergistically potentiated fungistatic efficacy of subinhibitory concentration of amphotericin B (AmB) and posaconazole (POS). ATRA also enhanced macrophagic phagocytosis of conidia. In a rat model of IPA, ATRA reduced mortality similarly to posaconazole. Fungistatic efficacy of ATRA alone and synergistically with other antifungal drugs was documented in vitro, likely by inhibiting fungal heat shock protein 90 (Hsp90) expression and Hsp90-related genes. ATRA treatment reduced mortality in a model of IPA in vivo Those findings suggest ATRA as a suitable fungistatic agent that can also reduce dosage and adverse reactions of classical antifungal drugs and add to the development of new therapeutic strategies against IPA and systemic fungal infections.

Predictive role of vitamin A serum concentration in psoriatic patients treated with IL-17 inhibitors to prevent skin and systemic fungal infections.

The use of biological drugs in psoriasis is replacing traditional therapies due to their specific mechanism and limited side effects. However, the use of Interleukin 17 inhibitors and the modification of its cytokine pathway could favor the risk of fungal infections. All-trans retinoic acid is an active metabolite of vitamin A with anti-inflammatory and immunoregulatory properties through its capacity to stimulate both innate and adaptive immunity and to its effects on proliferation, differentiation and apoptosis in a variety of immune cells. Furthermore, it has been recently discovered that All-trans retinoic acid has a direct fungistatic effect against Candida and Aspergillus Fumigatus. On the basis of these new insights, in the current review, we suggest that the evaluation of serum level of All-trans retinoic acid or vitamin A should be considered as a predictive marker for the development of fungal infections among psoriatic patients treated with Interleukin 17 inhibitors. In clinical practice, vitamin A test could be added in the routine hospital diagnostic management for a better selection of psoriatic patients eligible to Interleukin 17 inhibitors.

High-Risk Recurrence Basal Cell Carcinoma: Focus on Hedgehog Pathway Inhibitors and Review of the Literature.

Basal cell carcinoma is the most common skin tumour, with the majority of the cases occurring on the head and neck district, where cosmetic and functional results are crucial. It can be locally destructive if not diagnosed early and treated appropriately. Surgery is the treatment of choice for most lesions, but aggressive, recurrent, or unresectable tumours can be challenging to manage. Advanced basal cell carcinoma includes high recurrence risk subtypes, in which standard therapies demonstrate lack of efficacy. This led to a need for investigating more deeply the pathogenesis of the disease and to the discovery of the implication of the hedgehog pathway. The development of systemic inhibitors of this pathway provides new treatment options for patients with advanced disease, resulting in survival improvement. Food and Drug Administration, before, and European Medicines Agency later approved 2 Hedgehog pathway inhibitors for the treatment of advanced basal cell carcinomas, vismodegib and sonidegib. Here, we present a review of the current English language literature trying to analyze differences in the 2 drugs as a head-to-head comparison between them has not already been documented in a randomized controlled clinical trial. Although vismodegib and sonidegib showed similar efficacy and safety profiles, in an indirect comparison scenario, sonidegib has shown slightly better outcomes in locally advanced basal cell carcinoma than vismodegib. They present different molecular structures, as they bind different residues on their targets and develop resistance for different mutations. In a future scenario, clinical trials comparing the 2 drugs are needed, as well as expanding data on discontinuation of therapy and/or consequential administration of them, with the aim to improve our clinical practise.

Lactoferrin as Protective Natural Barrier of Respiratory and Intestinal Mucosa against Coronavirus Infection and Inflammation.

Recently, the world has been dealing with a devastating global pandemic coronavirus infection, with more than 12 million infected worldwide and over 300,000 deaths as of May 15th 2020, related to a novel coronavirus (2019-nCoV), characterized by a spherical morphology and identified through next-generation sequencing. Although the respiratory tract is the primary portal of entry of SARS-CoV-2, gastrointestinal involvement associated with nausea, vomiting and diarrhoea may also occur. No drug or vaccine has been approved due to the absence of evidence deriving from rigorous clinical trials. Increasing interest has been highlighted on the possible preventative role and adjunct treatment of lactoferrin, glycoprotein of human secretions part of a non-specific defensive system, known to play a crucial role against microbial and viral infections and exerting anti-inflammatory effects on different mucosal surfaces and able to regulate iron metabolism. In this review, analysing lactoferrin properties, we propose designing a clinical trial to evaluate and verify its effect using a dual combination treatment with local, solubilized intranasal spray formulation and oral administration. Lactoferrin could counteract the coronavirus infection and inflammation, acting either as natural barrier of both respiratory and intestinal mucosa or reverting the iron disorders related to the viral colonization.

Clindamycin versus clindamycin plus rifampicin in hidradenitis suppurativa treatment: Clinical and ultrasound observations.

BACKGROUND: Antibiotics are recognized as first-line treatments for hidradenitis suppurativa (HS), but the data on their efficacy are limited. OBJECTIVE: Evaluate the efficacy of oral clindamycin versus that of clindamycin plus rifampicin in patients with HS. METHODS: A total of 60 patients with mild-to-moderate-severe HS who were classified according to their International Hidradenitis Suppurativa Severity Score System (IHS4) and Hurley scores, were subdivided into 2 groups of 30 patients each (group A, the members of which received clindamycin plus rifampicin, and group B, the members of which were treated with clindamycin alone) and retrospectively studied. The main objective was to evaluate and compare the clinical and ultrasound responses between the groups after 8 weeks of treatment according to the Hidradenitis Suppurativa Clinical Response measure. RESULTS: After the treatment, 17 of 30 patients in group A and 19 of 30 in group B met the primary outcome. Both groups showed a similar improvement of IHS4 score, whereas the Dermatology Life Quality Index and pain Visual Analogue Scale scores improved more in group B. In particular, the reductions in nodule and abscess counts were similar between the 2 groups, whereas the number of draining tunnels decreased more in group B. The factors significantly associated with Hidradenitis Suppurativa Clinical Response score were age, body mass index, IHS4 score, and absence of axillary involvement. Disease-free survival was similar between the 2 groups. LIMITATIONS: The study was not randomized or placebo-controlled. CONCLUSION: Clindamycin may be a useful treatment alternative to antibiotic combination regardless of HS clinical stage.

Efficacy of PTX3 and posaconazole combination in a rat model of invasive pulmonary aspergillosis.

Posaconazole is currently used for the prophylaxis of invasive pulmonary aspergillosis (IPA). Limitations to posaconazole usage are drug-drug interactions and side effects. PTX3 is an innate immunity glycoprotein with opsonic activity, proven to be protective in IPA animal models. This study investigated the combination of posaconazole with PTX3. The results indicate synergy between PTX3 and posaconazole against aspergillosis, suggesting that a combination of reduced doses of posaconazole with the immune response enhancer PTX3 might represent a treatment option with a higher therapeutic index than posaconazole.

Synergistic Effect of Metronidazole and Chlorhexidine against Porphyromonas gingivalis Growth: An In Vitro Study.

Aim: To evaluate the potential synergistic activity of metronidazole (MTZ) and chlorhexidine (CHX) against Porphyromonas. gingivalis (P. gingivalis) growth. Methods: Antimicrobial susceptibility tests of P. gingivalis to MTZ and CHX were performed on in vitro serial 2-fold dilutions of MTZ (from 1 mg/mL to 0.015 mg/mL) and CHX (from 1 mg/mL to 0.03 mg/mL) in thioglycollate medium broth in a 96-well plate. The turbidity of each sample was analyzed by absorbance spectrophotometry at 450 nm wavelengths by using an enzyme-linked immunosorbent assay (ELISA) reader. The MIC50 (minimum inhibitory concentration) and MBC (minimum bactericidal concentration) were assessed. To investigate the potential synergism between MTZ and CHX, bacterial cells were treated with MTZ or CHX, as described above, either alone or in combination. Results: The MIC50 of MTZ was 0.03 mg/mL while that of CHX ranged from 0.12 to 0.06 mg/mL. MTZ and CHX exerted a significant inhibitory effect on P. gingivalis growth in a dose-dependent manner. MTZ at a low and ineffective concentration of 0.015 mg/mL, associated with a suboptimal concentration of CHX (0.03 mg/mL), exhibited a significant synergistic inhibitory effect on bacterial growth (50% inhibition vs. control) (p < 0.001), and the effect was more remarkable with 0.06 mg/mL CHX (75% inhibition vs. control). Conclusions: CHX and MTZ showed a significant synergistic effect against P. gingivalis growth. A non-effective concentration of MTZ (0.015 mg/mL) combined with suboptimal concentrations of CHX (0.03 mg/mL and 0.06 mg/mL) were related to a 50% growth in the inhibition and 99.99% death of P. gingivalis, respectively. The applicability of the clinical use of these concentrations should be tested in randomized controlled trials.

Malassezia furfur bloodstream infection: still a diagnostic challenge in clinical practice.

The opportunistic fungus Malassezia furfur (M. furfur) can cause either cutaneous or systemic infections. We report a case of M. furfur fungemia in a 22-year-old male with T-cell Acute Lymphoblastic Leukemia (T-ALL) who developed concomitant Bacillus cereus (B. cereus) septicemia. The fungal infection was diagnosed by microscopic examination and culture-based methods, while automated blood culture systems and molecular approaches failed in identifying the fungus. Despite appropriate therapy, the patient died 18 days after the hospitalization.

Stephanoascus ciferrii Complex: The Current State of Infections and Drug Resistance in Humans.

In recent years, the incidence of fungal infections in humans has increased dramatically, accompanied by an expansion in the number of species implicated as etiological agents, especially environmental fungi never involved before in human infection. Among fungal pathogens, Candida species are the most common opportunistic fungi that can cause local and systemic infections, especially in immunocompromised individuals. Candida albicans (C. albicans) is the most common causative agent of mucosal and healthcare-associated systemic infections. However, during recent decades, there has been a worrying increase in the number of emerging multi-drug-resistant non-albicans Candida (NAC) species, i.e., C. glabrata, C. parapsilosis, C. tropicalis, C. krusei, C. auris, and C. ciferrii. In particular, Candida ciferrii, also known as Stephanoascus ciferrii or Trichomonascus ciferrii, is a heterothallic ascomycete yeast-like fungus that has received attention in recent decades as a cause of local and systemic fungal diseases. Today, the new definition of the S. ciferrii complex, which consists of S. ciferrii, Candida allociferrii, and Candida mucifera, was proposed after sequencing the 18S rRNA gene. Currently, the S. ciferrii complex is mostly associated with non-severe ear and eye infections, although a few cases of severe candidemia have been reported in immunocompromised individuals. Low susceptibility to currently available antifungal drugs is a rising concern, especially in NAC species. In this regard, a high rate of resistance to azoles and more recently also to echinocandins has emerged in the S. ciferrii complex. This review focuses on epidemiological, biological, and clinical aspects of the S. ciferrii complex, including its pathogenicity and drug resistance.

Apremilast as a Potential Targeted Therapy for Metabolic Syndrome in Patients with Psoriasis: An Observational Analysis.

Psoriasis (PsO) is a chronic inflammatory dermatosis that often presents with erythematous, sharply demarcated lesions. Although psoriasis is primarily a dermatological disease, its immune-mediated pathogenesis produces systemic effects and is closely associated with various comorbid conditions such as cardiovascular disease (CVD), metabolic syndrome (MetS), and diabetes mellitus type II (DMII). Apremilast, an oral phosphodiesterase 4 (PDE-4) inhibitor, has shown promise in treating moderate-to-severe psoriasis and is associated with potential cardiometabolic benefits. In a 12-month prospective observational study involving 137 patients with moderate-to-severe psoriasis, we assessed changes in psoriasis clinimetric scores and metabolic profiles from baseline (T0) to 52 weeks (T1) to evaluate the efficacy of apremilast. After 52 weeks of apremilast treatment, we documented a statistically significant decrease in low-density lipoprotein (LDL) and total cholesterol, triglycerides, and glucose levels. Our findings even suggest a potential synergistic effect among patients treated with apremilast, alongside concomitant statin and/or insulin therapy. Although the results of our study must be validated on a larger scale, the use of apremilast in the treatment of psoriatic patients with cardio-metabolic comorbidities yields promising results.

Screening of Klebsiella pneumoniae subsp. pneumoniae Strains with Multi-Drug Resistance and Virulence Profiles Isolated from an Italian Hospital between 2020 and 2023.

Klebsiella pneumoniae strains that are resistant to multiple drugs (KPMDRs), which are often acquired in hospital settings and lead to healthcare-associated infections, pose a serious public health threat, as does hypervirulent K. pneumoniae (hvKp), which can also cause serious infections in otherwise healthy individuals. The widespread and often unnecessary use of antibiotics seen during the recent COVID-19 pandemic has exacerbated the challenges posed by antibiotic resistance in clinical settings. There is growing concern that hypervirulent (hvKp) strains may acquire genes that confer antimicrobial resistance, thus combining an MDR profile with their increased ability to spread to multiple body sites, causing difficult-to-treat infections. This study aimed to compare resistance and virulence profiles in KPC-3-producing K. pneumoniae isolates collected over four years (2020-2023). A genome-based surveillance of all MDR CRE-K. pneumoniae was used to identify genetic differences and to characterize the virulence and resistance profiles. Our results provide a picture of the evolution of resistance and virulence genes and contribute to avoiding the possible spread of isolates with characteristics of multi-drug resistance and increased virulence, which are thought to be one of the main global challenges to public health, within our hospital.

The Interplay between Candida albicans, Vaginal Mucosa, Host Immunity and Resident Microbiota in Health and Disease: An Overview and Future Perspectives.

Vulvovaginal candidiasis (VVC), which is primarily caused by Candida albicans, is an infection that affects up to 75% of all reproductive-age women worldwide. Recurrent VVC (RVVC) is defined as >3 episodes per year and affects nearly 8% of women globally. At mucosal sites of the vagina, a delicate and complex balance exists between Candida spp., host immunity and local microbial communities. In fact, both immune response and microbiota composition play a central role in counteracting overgrowth of the fungus and maintaining homeostasis in the host. If this balance is perturbed, the conditions may favor C. albicans overgrowth and the yeast-to-hyphal transition, predisposing the host to VVC. To date, the factors that affect the equilibrium between Candida spp. and the host and drive the transition from C. albicans commensalism to pathogenicity are not yet fully understood. Understanding the host- and fungus-related factors that drive VVC pathogenesis is of paramount importance for the development of adequate therapeutic interventions to combat this common genital infection. This review focuses on the latest advances in the pathogenic mechanisms implicated in the onset of VVC and also discusses novel potential strategies, with a special focus on the use of probiotics and vaginal microbiota transplantation in the treatment and/or prevention of recurrent VVC.

Rapid System to Detect Variants of SARS-CoV-2 in Nasopharyngeal Swabs.

Currently, the reference method for identifying the presence of variants of SARS-CoV-2 is whole genome sequencing. Although it is less expensive than in the past, it is still time-consuming, and interpreting the results is difficult, requiring staff with specific skills who are not always available in diagnostic laboratories. The test presented in this study aimed to detect, using traditional real-time PCR, the presence of the main variants described for the spike protein of the SARS-CoV-2 genome. The primers and probes were designed to detect the main deletions that characterize the different variants. The amplification targets were deletions in the S gene: 25-27, 69-70, 241-243, and 157-158. In the ORF1a gene, the deletion 3675-3677 was chosen. Some of these mutations can be considered specific variants, while others can be identified by the simultaneous presence of one or more deletions. We avoided using point mutations in order to improve the speed of the test. Our test can help clinical and medical microbiologists quickly recognize the presence of variants in biological samples (particularly nasopharyngeal swabs). The test can also be used to identify variants of the virus that could potentially be more diffusive as well as not responsive to the vaccine.

Green Nail Syndrome Treated with Ozenoxacin: Two Case Reports.

Green nail syndrome (GNS) is a persistent greenish pigmentation of the nail plate, originally described in 1944 by Goldman and Fox, due to Pseudomonas aeruginosa infection. Recently, pulmonary co-infection of P. aeruginosa and Achromobacter spp. has been described in patients with cystic fibrosis. Achromobacter xylosoxidans is a multidrug-resistant (MDR) pathogen involved in lung and soft tissue skin infections. Both Achromobacter xylosoxidans and P. aeruginosa are mainly found in humid environments or in water. There are no recognized co-infections due to P. aeruginosa and A. xylosoxidans in the skin and appendages. We describe two cases of GNS, the first due to P. aeruginosa associated with Achromobacter xylosoxidans; the other due to MDR P. aeruginosa, both successfully treated with topical ozenoxacin 1% cream daily for 12 weeks. The clinical management of GNS can be confusing, especially when the bacterial culture result is inconsistent or when non-Pseudomonas bacteria are isolated. In our case, due to the co-infection of P. aeruginosa and Achromobacter spp., local treatment with ozenoxacin - the first nonfluorinated quinolone - could be a safe and effective treatment in case of MDR nail infections. Further studies are required to evaluate clinical isolation from nail infections and the co-presence of P. aeruginosa and A. xylosoxidans.

Closing the Gap in Proteomic Identification of Histoplasma capsulatum: A Case Report and Review of Literature.

Histoplasmosis is a globally distributed systemic infection caused by the dimorphic fungus Histoplasma capsulatum (H. capsulatum). This fungus can cause a wide spectrum of clinical manifestations, and the diagnosis of progressive disseminated histoplasmosis is often a challenge for clinicians. Although microscopy and culture remain the gold standard diagnostic tests for Histoplasma identification, matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS) has emerged as a method of microbial identification suitable for the confirmation of dimorphic fungi. However, to our knowledge, there are no entries for H. capsulatum spectra in most commercial databases. In this review, we describe the case of disseminated histoplasmosis in a patient living with HIV admitted to our university hospital that we failed to identify by the MALDI-TOF method due to the limited reference spectrum of the instrument database. Furthermore, we highlight the utility of molecular approaches, such as conventional polymerase chain reaction (PCR) and DNA sequencing, as alternative confirmatory tests to MALDI-TOF technology for identifying H. capsulatum from positive cultures. An overview of current evidence and limitations of MALDI-TOF-based characterization of H. capsulatum is also presented.

Antitumor effects of the benzophenanthridine alkaloid sanguinarine in a rat syngeneic model of colorectal cancer.

To evaluate the in-vivo preclinical antitumor activity of sanguinarine in a rat syngeneic model of colorectal cancer. The effects of sanguinarine on DHD/K12/TRb colorectal adenocarcinoma cells were first evaluated in vitro by means of ³H-thymidine incorporation, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS) assay, and terminal transferase dUTP nick end labeling (TUNEL) microscopy. For the in-vivo studies, DHD/K12/TRb cells (1.5 × 106 cells/0.3 ml of sterile saline/animal) were injected subcutaneously in syngeneic BDIX rats, which were chronically treated with sanguinarine (5 mg/kg/day per os) or control diluent. Tumor growth, body weight, hematologic, and clinical chemistry measurements were monitored in individual animals at defined time intervals. After killing, subcutaneous tumors were explanted from experimental animals for histopathological examination. In vitro, micromolar concentrations of sanguinarine inhibited dose-dependently DHD/K12/TRb cell proliferation and metabolism and induced cell death by apoptosis. In vivo, oral administration of sanguinarine induced a significant inhibition of tumor growth (P<0.01 vs. untreated controls), in the absence of any toxic or side effects. Marked apoptosis and reduced peritumoral vascularization were observed in tumors from sanguinarine-treated rats as compared with the controls. Additional basic studies are needed to fully characterize the mechanism/s underlying the inhibitory effects of sanguinarine on angiogenesis and tumor growth as well as the pharmacological and safety profile of this drug in experimental tumor models. Overall, findings from this study suggest that sanguinarine is a likely candidate for further evaluation in cancer therapy.

Interaction of Pelargonium sidoides Compounds with Lactoferrin and SARS-CoV-2: Insights from Molecular Simulations.

(1) Background: Pelargonium sidoides extracts and lactoferrin are two important natural, anti-inflammatory, and antiviral agents, which can interfere with the early stages of SARS-CoV-2 infection. Molecular docking and molecular dynamics simulation approaches have been applied to check for the occurrence of interactions of the Pelargonium sidoides compounds with lactoferrin and with SARS-CoV-2 components. (2) Methods: Computational methods have been applied to confirm the hypothesis of a direct interaction between PEL compounds and the lactoferrin protein and between Pelargonium sidoides compounds and SARS-CoV-2 Spike, 3CLPro, RdRp proteins, and membrane. Selected high-score complexes were structurally investigated through classical molecular dynamics simulation, while the interaction energies were evaluated using the molecular mechanics energies combined with generalized Born and surface area continuum solvation method. (3) Results: Computational analyses suggested that Pelargonium sidoides extracts can interact with lactoferrin without altering its structural and dynamical properties. Furthermore, Pelargonium sidoides compounds should have the ability to interfere with the Spike glycoprotein, the 3CLPro, and the lipid membrane, probably affecting the functional properties of the proteins inserted in the double layer. (4) Conclusion: Our findings suggest that Pelargonium sidoides may interfere with the mechanism of infection of SARS-CoV-2, especially in the early stages.