Arachne

Arachn

According to mythology, Arachne was a human woman who challenged the goddess Athena to a weaving competition. As punishment for her vanity, Athena cursed her with guilt and Arachne hung herself. The goddess felt bad and brought her back as a spider, to weave for eternity. While the Supernatural plot doesn't go into this, we do see spider-humans who try to breed by changing humans of the opposite sex into spiders, thanks to a bite.

Sam hunted one Arachne while he was soulless and he killed all the other humans affected. Now, with a soul in Unforgiven, he returns to the same town and finds that a new Arachne is hunting. . . the humans he thought he killed were already turned when he shot them.

According to the show, Arachnes can be killed by beheading, but are bullet and fire resistant