Highlights We developed a controlled assay to investigate the UV-C inactivation kinetics for SARS-CoV-2. We established the UV-C lethal doses for the virus in vitro . LD 90 for SARS-CoV-2 was reached at 0.016 mJ/cm 2 . LD 99.999 was achieved at 108.714 mJ/cm 2 with exposure time less than 50 s.

Background The hyaluronidase enzyme is generally known as a spreading factor in animal venoms. Although its activity has been demonstrated in several organisms, a deeper knowledge about hyaluronidase and the venom spreading process from the bite/sting site until its elimination from the victim's body is still in need. Herein, we further pursued the goal of demonstrating the effects of inhibition of T . serrulatus venom (TsV) hyaluronidase on venom biodistribution. Methods and principal findings We used technetium-99m radiolabeled Tityus serrulatus venom ( 99m Tc-TsV) to evaluate the venom distribution kinetics in mice. To understand the hyaluronidase’s role in the venom’s biodistribution, 99m Tc-TsV was immunoneutralized with specific anti- T . serrulatus hyaluronidase serum. Venom biodistribution was monitored by scintigraphic images of treated animals and by measuring radioactivity levels in tissues as heart, liver, lungs, spleen, thyroid, and kidneys. In general, results revealed that hyaluronidase inhibition delays venom components distribution, when compared to the non-neutralized 99m Tc-TsV control group. Scintigraphic images showed that the majority of the immunoneutralized venom is retained at the injection site, whereas non-treated venom is quickly biodistributed throughout the animal’s body. At the first 30 min, concentration peaks are observed in the heart, liver, lungs, spleen, and thyroid, which gradually decreases over time. On the other hand, immunoneutralized 99m Tc-TsV takes 240 min to reach high concentrations in the organs. A higher concentration of immunoneutralized 99m Tc-TsV was observed in the kidneys in comparison with the non-treated venom. Further, in situ neutralization of 99m Tc-TsV by anti- T . serrulatus hyaluronidase serum at zero, ten, and 30 min post venom injection showed that late inhibition of hyaluronidase can still affect venom biodistribution. In this assay, immunoneutralized 99m Tc-TsV was accumulated in the bloodstream until 120 or 240 min after TsV injection, depending on anti-hyaluronidase administration time. Altogether, our data show that immunoneutralization of hyaluronidase prevents venom spreading from the injection site. Conclusions By comparing TsV biodistribution in the absence or presence of anti-hyaluronidase serum, the results obtained in the present work show that hyaluronidase has a key role not only in the venom spreading from the inoculation point to the bloodstream, but also in venom biodistribution from the bloodstream to target organs. Our findings demonstrate that hyaluronidase i...

The disease caused by SARS-CoV2, covid-19, rapidly spreads worldwide, causing the greatest threat to global public health in the last 100 years. This scenario has become catastrophic as there are no approved vaccines to prevent the disease, and the main measures to contain the virus transmission are confinement and social distancing. One priority strategy is based on drug repurposing by pursuing antiviral chemotherapy that can control transmission and prevent complications associated with covid-19. With this aim, we performed a high content screening assay for the discovery of anti-SARS-CoV-2 compounds. From the 65 screened compounds, we have found four drugs capable to selectively inhibit SARS-CoV-2 in vitro infection: brequinar, abiraterone acetate, neomycin, and the extract of Hedera helix. Brequinar and abiraterone acetate had higher inhibition potency against SARS-CoV-2 than neomycin and Hedera helix extract, respectively. Drugs with reported antiviral activity and in clinical trials for covid-19, chloroquine, ivermectin, and nitazoxanide, were also included in the screening, and the last two were found to be non-selective. We used a data mining approach to build drug- host molecules-biological function-disease networks to show in a holistic way how each compound is interconnected with host node molecules and virus infection, replication, inflammatory response, and cell apoptosis. In summary, the present manuscript identified four drugs with active inhibition effect on SARS-CoV-2 in vitro infection, and by network analysis, we provided new insights and starting points for the clinical evaluation and repurposing process to treat SARS-CoV-2 infection.

Scorpion sting envenoming impacts millions of people worldwide, with cardiac effects being one of the main causes of death on victims. Here we describe the first Ca2+ channel toxin present in Tityus serrulatus (Ts) venom, a cell penetrating peptide (CPP) named CPP-Ts. We show that CPP-Ts increases intracellular Ca2+ release through the activation of nuclear InsP3R of cardiomyocytes, thereby causing an increase in the contraction frequency of these cells. Besides proposing a novel subfamily of Ca2+ active toxins, we investigated its potential use as a drug delivery system targeting cancer cell nucleus using CPP-Ts’s nuclear-targeting property. To this end, we prepared a synthetic CPP-Ts sub peptide14–39 lacking pharmacological activity which was directed to the nucleus of specific cancer cell lines. This research identifies a novel subfamily of Ca2+ active toxins and provides new insights into biotechnological applications of animal venoms.

37Background: 38 The hyaluronidase enzyme is generally known as a spreading factor in 39 animal venoms. Although its activity has been demonstrated in several 40 organisms, a deeper knowledge about hyaluronidase and the venom spreading 41 process from the bite/sting site until its elimination from the victim's body is still in 42 need. 43Methods and principal findings: 44 We used technetium-99m radiolabeled Tityus serrulatus venom ( 99m Tc-45 TsV) to evaluate the venom distribution kinetics in mice. To understand the 46 hyaluronidase's role in the venom's biodistribution, 99m Tc-TsV was 47 immunoneutralized with specific anti-T.serrulatus hyaluronidase serum. Venom 48 biodistribution was monitored by scintigraphic images of treated animals and by 49 measuring radioactivity levels in tissues as heart, liver, lungs, spleen, thyroid, and 50 kidneys. In general, results revealed that hyaluronidase inhibition delays venom 51 components distribution, when compared to the non-neutralized 99m Tc-TsV 52 control group. Scintigraphic images showed that the majority of the 53 immunoneutralized venom is retained at the injection site, whereas non-treated 54 venom is quickly biodistributed throughout the animal's body. At the first 30 55 minutes, concentration peaks are observed in the heart, liver, lungs, spleen, and 56 thyroid, which gradually decreases over time. On the other hand, 57 immunoneutralized 99m Tc-TsV takes 240 minutes to reach high concentrations in 58 the organs. A higher concentration of immunoneutralized 99m Tc-TsV was 59 observed in the kidneys in comparison with the non-treated venom. Further, in 60 situ neutralization of 99m Tc-TsV by anti-T.serrulatus hyaluronidase serum at zero, 61 ten, and 30 minutes post venom injection showed that late inhibition of 62 hyaluronidase can still affect venom biodistribution. In this assay, 63 immunoneutralized 99m Tc-TsV was accumulated in the bloodstream until 120 or 64 240 minutes after TsV injection, depending on anti-hyaluronidase administration 65 time. Altogether, our data show that immunoneutralization of hyaluronidase 66 prevents venom spreading from the injection site.67Conclusions: 68 The results obtained in the present work show that hyaluronidase has a 69 key role not only in the venom spreading from the inoculation point to the 70 bloodstream, but also in venom biodistribution from the bloodstream to target 71 organs. Our findings demonstrate that hyaluronidase is indeed an important 72 spreading factor of TsV, and its inhibition can be used as a novel first-aid strategy 73 in envenoming. 74 Author summary 75 Hyaluronidases are known as the venom components responsible for 76 disseminating toxins from the injection site to the victim's organism. Therefore, 77 understanding how the venom distribution occurs and the role of hyaluronidases 78 in this process is crucial in the field of toxinology. In this study, we inhibited Tityus 79 serrulatus venom (TsV) hyaluronidase's action using specific anti-Ts-80 hyaluronidase antibodies. Labeling TsV with a r...